Tinnitus Treatment Report

www.TinnitusTreatmentReport.com

admin

Striatal networks for tinnitus treatment targeting

CATEGORY:
Research

TITLE:
Striatal networks for tinnitus treatment targeting

DESCRIPTION:
Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased…

CONTENT:
Hum Brain Mapp. 2021 Oct 5. doi: 10.1002/hbm.25676. Online ahead of print.

ABSTRACT

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl’s gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.

PMID:34609038 | DOI:10.1002/hbm.25676

SOURCE:
Human brain mapping

DATE – PUBLISHED:
2021-10-07T16:02:18Z

DATE – DOI: 2021-10-07T16:02:18Z
DATE – PUBMED: 2021 Oct 5
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 05 Oct 2021 06:00:00 -0400

DATE – RETRIEVED:
10/09/21 09:57AM
2021-10-09T09:57:21-04:00

IDENTIFIER:
pmid:34609038,doi:10.1002/hbm.25676

PUBMED ID:
pubmed:34609038

DOI:
10.1002/hbm.25676

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34609038/

LINK – DOI:
https://doi.org/10.1002/hbm.25676

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/hbm.25676

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-10-09T09:57:21-04:00, www.tinnitustreatmentreport.com.

Effects of two inhibitors of metabolic glutamate receptor 5 on mice with tinnitus

CATEGORY:
Research

TITLE:
Effects of two inhibitors of metabolic glutamate receptor 5 on expression of endogenous homer scaffold protein 1 in the auditory cortex of mice with tinnitus

DESCRIPTION:
Tinnitus is deemed as the result of abnormal neural activities in the brain, and Homer proteins are expressed in the brain that convey nociception. The expression of Homer in tinnitus has not been studied. We hypothesized that expression of Homer in the auditory cortex was altered after tinnitus treatment. Mice were injected with sodium salicylate to induce tinnitus. Expression of Homer was detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry…

CONTENT:
Bioengineered. 2021 Dec;12(1):7156-7164. doi: 10.1080/21655979.2021.1979354.

ABSTRACT

Tinnitus is deemed as the result of abnormal neural activities in the brain, and Homer proteins are expressed in the brain that convey nociception. The expression of Homer in tinnitus has not been studied. We hypothesized that expression of Homer in the auditory cortex was altered after tinnitus treatment. Mice were injected with sodium salicylate to induce tinnitus. Expression of Homer was detected by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry assays. We found that Homer1 expression was upregulated in the auditory cortex of mice with tinnitus, while expression of Homer2 or Homer3 exhibited no significant alteration. Effects of two inhibitors of metabolic glutamate receptor 5 (mGluR5), noncompetitive 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) and competitive α-methyl-4-carboxyphenylglycine (MCPG), on the tinnitus scores of the mice and on Homer1 expression were detected. MPEP significantly reduced tinnitus scores and suppressed Homer1 expression in a concentration dependent manner. MCPG had no significant effects on tinnitus scores or Homer1 expression. In conclusion, Homer1 expression was upregulated in the auditory cortex of mice after tinnitus, and was suppressed by noncompetitive mGluR5 inhibitor MPEP, but not competitive mGluR5 inhibitor MCPG.

PMID:34546852 | DOI:10.1080/21655979.2021.1979354

SOURCE:
Bioengineered

DATE – PUBLISHED:
2021-09-21T18:28:57Z

DATE – DOI: 2021-09-21T18:28:57Z
DATE – PUBMED:
DATE OUTPUT MATCHED: False

DATE – ADDED:
Tue, 21 Sep 2021 06:00:00 -0400

DATE – RETRIEVED:
09/21/21 07:06PM
2021-09-21T19:06:35-04:00

IDENTIFIER:
pmid:34546852,doi:10.1080/21655979.2021.1979354

PUBMED ID:
pubmed:34546852

DOI:
10.1080/21655979.2021.1979354

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34546852/

LINK – DOI:
https://doi.org/10.1080/21655979.2021.1979354

LINK – PUBLISHER:
https://www.tandfonline.com/doi/full/10.1080/21655979.2021.1979354

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-09-21T19:06:35-04:00, www.tinnitustreatmentreport.com.

Susan Shore’s New “Auricle Device” for Tinnitus Is Almost Ready for Commercial Release…

The breakthrough device — based on 20 years of Shore’s research and $14 million in funding — is “nearly market ready,” according to Auricle Inc CEO and Co-Founder, Jon Pearson.

Auricle tinnitus logo
Logo for Susan Shore’s new medical device startup: Auricle Inc.

Here is the official product description (Auricle Inc):

Device that combines auditory frequencies and timed somatosensory stimuli to suppress tinnitus-generating neurons that cause ringing in the ears.

Here are the latest details — developing story:

  • Susan Shore recently co-founded a company called Auricle Inc.
  • Auricle Inc is a medical device venture (startup) created to commercialize Shore’s tinnitus device and patents.
  • The company was formed with the approval of the University of Michigan Reagents and there is an “Option Agreement” between the university and Auricle Inc.
  • The domain name for Auricle Inc (www.auricleinc.com) is registered and associated with the company. No website has been created yet (as of September 7, 2021, 1:28pm EST).

Excerpt from the agreement:

“… a for-profit company called Auricle Inc. (the “Company”). The Company was formed recently to commercialize a device to treat tinnitus…”

Susan Shore, PhD, a Professor in the Department of Otolaryngology-Head and Neck Surgery, and David Martel, Graduate Student Research Assistant in the Department of Otolaryngology-Head and Neck Surgery, are partial owners of a for-profit company called Auricle Inc. (the “Company”). The Company was formed recently to commercialize a device to treat tinnitus and desires to option from the University of Michigan the University’s rights associated with the following technology:

UM OTT File No. 5507, entitled: “Tailored Auditory – Somatosensory Stimulation to Treat Tinnitus” (Inventors: Seth Koehler, David Martel, Susan Shore)

The Office of Technology Transfer selected the Company as a University partner and negotiated the terms of the proposed Agreement in accordance with University policy and its accepted licensing principles.

Here is the Gen 2.0 clinical unit (i.e., the one that was used in the latest Shore clinical trial, it would seem)… which might give us some idea of the Auricle device product hardware (note: no confirmation yet on what the market-ready device will look like).

Auricle device demo product by Susan Shore

In addition…

Billy Mays Susan Shore Meme

Video: 2-Minute Auricle Inc Tinnitus Device Investor Pitch

The unlisted video, “Auricle 2 min 2021 Rosenman Innovator Demo Day AU I0F2VG4”, only has 45 views at the time of this writing (September 7, 2021, 1:29pm EST). Also worth mentioning are the social signals: the video currently has one Like and one comment… both of which can be traced to a mysterious “Michael Sutton” character. Hmmmm…

This is a developing story. Expect more updates soon. Sources below. Remember to subscribe. And please share, if you want to encourage more “exclusive” updates like this one.

More to follow…

“No official release date yet. As soon as I know more, I will email the list.”
– Michael

Get Email Updates

Subscribe to the Tinnitus Treatment Report email newsletter to stay informed about the release date for Susan Shore’s Auricle Device for tinnitus. Plus, other promising new tinnitus treatments on the horizon. It’s free, you get one or two emails per week (but only when something interesting is happening). No sneaky third party emails. Privacy respected. Unsubscribe any time with one click.

References

  • https://techtransfer.umich.edu/companies/auricle-inc/
  • https://innovation.medicine.umich.edu/portfolio_post/shore/
  • https://rosenmaninstitute.org/portfolio/auricle/
  • more sources will be added as this article is expanded

The role of vitamin D in subjective tinnitus: findings suggest vitamin D level correlates with tinnitus impact

CATEGORY:
Research

TITLE:
The role of vitamin D in subjective tinnitus-A case-control study

DESCRIPTION:
Regarding the high prevalence of vitamin D (25(OH)D) deficiency in the population and its possible association with ear diseases, we aimed to investigate the 25(OH)Dserum level in patients with subjective, nonpulsating tinnitus and its effect on tinnitus severity. The study included 201 tinnitus patients and 99 controls. Patient clinical information, including tinnitus characteristics and severity according to Tinnitus Handicap Inventory (THI), loudness assessed by Visual Analogue Scale (VAS),…

CONTENT:
PLoS One. 2021 Aug 18;16(8):e0255482. doi: 10.1371/journal.pone.0255482. eCollection 2021.

ABSTRACT

Regarding the high prevalence of vitamin D (25(OH)D) deficiency in the population and its possible association with ear diseases, we aimed to investigate the 25(OH)Dserum level in patients with subjective, nonpulsating tinnitus and its effect on tinnitus severity. The study included 201 tinnitus patients and 99 controls. Patient clinical information, including tinnitus characteristics and severity according to Tinnitus Handicap Inventory (THI), loudness assessed by Visual Analogue Scale (VAS), audiometry, and the blood level of vitamin D, was recorded. The level of 25(OH)D in tinnitus patients was significantly decreased compared with the controls (19.86 ± 7.53 and 27.43 ± 8.85 ng/ml, respectively; P value < 0.0001). More patients in the tinnitus group were deficient in vitamin D, compared with the controls (50.7% vs. 22.2% respectively, p < 0.0001). Tinnitus patients with a lower serum level of 25(OH)D (≤15 ng/dl) were significantly younger, had a higher degree of tinnitus severity measured with THI and VAS scales, had higher triglyceride and TSH levels, and a lower HDL level compared with individuals who had higher 25(OH)D level (>15 ng/dl). There was a strong correlation between the 25(OH)D level and THI. Our findings suggest that a large proportion of tinnitus patients suffers from vitamin D deficiency and that the vitamin D level correlates with tinnitus impact. We recommend a vitamin D assessment for all tinnitus patients.

PMID:34407088 | DOI:10.1371/journal.pone.0255482

SOURCE:
PloS one

DATE – PUBLISHED:
2021-08-18T17:50:30Z

DATE – DOI: 2021-08-18T17:50:30Z
DATE – PUBMED: 2021 Aug 18
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 18 Aug 2021 06:00:00 -0400

DATE – RETRIEVED:
08/18/21 08:05PM
2021-08-18T20:05:30-04:00

IDENTIFIER:
pmid:34407088,doi:10.1371/journal.pone.0255482

PUBMED ID:
pubmed:34407088

DOI:
10.1371/journal.pone.0255482

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34407088/

LINK – DOI:
https://doi.org/10.1371/journal.pone.0255482

LINK – PUBLISHER:
https://dx.plos.org/10.1371/journal.pone.0255482

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-08-18T20:05:30-04:00, www.tinnitustreatmentreport.com.

First Look at 6B-001, 65Bio’s Preclinical Drug Candidate for the Treatment of Chronic Tinnitus

Some new information about 6B-001, a preclinical tinnitus (and hearing loss) drug that is currently being developed by 65Bio Inc, a biotech startup based in Wellesley, MA.

Here is what we know so far, starting with a description from the Product page of the 65Bio company website:

65Bio lead product is 6B-001 an orally available small molecule found to be well tolerated in human. 6B-001 is in preclinical development phase for the treatment of auditory pathologies. The initial focus is on the treatment of chronic tinnitus and the longer-term focus is on hearing loss and vertigo.

6B-001 appeared tinnitus meme

While this official description does not tell us very much about the drug… it does provide clues that can potentially reveal more details about the drug, and lead us to its [plausible] mechanisms i.e., how it might treat tinnitus and/or hearing loss, etc.

The raw facts:

  • 6B-001
  • orally available
  • small molecule
  • safe/tested in humans
  • tinnitus, hearing loss, vertigo, auditory pathologies

Together, these facts strongly suggest that we are probably looking for an existing drug that has completed phase 1 clinical trials and met safety endpoints. Which also means the drug is one that is being studied and tested for other health conditions… and “6B-001” is the codename for its tinnitus-related use.

Of course, those details alone do not narrow down the list of plausible 6B-001 candidates. What we need is a short list of possible drugs that “6B-001” might represent.

Fortunately, our hunt for this mystery drug becomes dramatically easier when we add certain constraints.

In this case, limiting our “suspects” to drugs that are currently being developed by other companies that are funded by the same group as 65Bio Inc. Follow the money…

So, we know that 65Bio Inc is backed by Extera Partners.

According to the Extera Partners website, Extera has a portfolio of biotech companies. And we can see that six of these companies are in the same category (“venture creation”) as 65Bio.

These other five companies are where we want to look for clues and connections… in hopes of finding drugs that seem like they might be strong candidates for treating tinnitus. According to existing research and known/suspected mechanisms… as well as overlapping health conditions that are often associated with tinnitus.

Put another way, we want to investigate the drug development pipelines of these five other companies… to see if we can find any drugs that might involve mechanisms/targets that are associated with tinnitus or hearing loss or vertigo…

By doing this, we might be able to identify which of these drugs is likeliest to be “6B-001” (or some variation of it, with a different name, for a different condition, or perhaps in combination with something else),

This approach assumes that 65Bio Inc is a “spinoff” of one of Extera’s properties. Created for the potential tinnitus-treating component (and auditory pathology related components) of a drug or drugs that are hiding somewhere in the pipelines of one or more of their portfolio companies.

The strong overlap between the people involved in 65Bio and these five other companies and Extera… is another reason why we suspect to find the drug identity within the Extera portfolio.

Sure enough, that seems to be the case.

At least, we now have some plausible candidates and clues.

COMMENT: As of right now [7/23/2021], I cannot confirm the mechanism behind 6B-001. But I have found some leads…

After reviewing the drug portfolios of the five other Extera Partners-backed ventures (Janus, Censa, Acatama, Acer, Intera), here is a list of some possible drugs/mechanisms/targets that are possibly related to 6B-001 — presented in no particular order:

  • anti-TLR drug (toll-like receptor antagonism) — autoimmune/inflammation connection + known overlap between tinnitus and Sjogren’s, SLE, etc..
  • vatiquinone, PTC743, EPI-743 — epilepsy + mitochondrial connection
  • PTC857, 15-lipoxygenase — inflammation/oxidative stress connection
  • unesbulin, PTC596, BMI-1 inhibitor — BMI-1 + hair cell connection
  • sepiapterin  — tetrahydrobiopterin disorder connection, autism overlap connection
  • TO BE CONTINUED [last updated: 7/23/2021 at 1:56 PM EST]
[Work in progress. Draft copy.]

This is an incomplete “short list” of possible drugs that might be repurposed for tinnitus and/or hearing loss or reformulated… and called “6B-001” (or 6B-002). Furthermore, this is unofficial information. It is patchy guesswork. As such, it should be considered nothing more than an educated and semi-structured form of good ol’ fashioned wild speculation.

Having said that, it also provides us with the raw ingredients to make sense of 6B-001… until 65Bio decides it is time to relieve us of our nagging curiosity… and issue a press release or add a couple more paragraphs to their website. (If anyone reading wants to email them and ask “What is the mechanism behind 6B-001 for chronic tinnitus?”, have at it: admin@65bio.com) Oh, and if anyone does this… and forwards me the reply… I will happily send them a copy of my next email newsletter anywhere from 12-24 hours before I email it to everyone else. (Super ultra early access, or whatever you want to call it.)

Last but not least… since I have not had the time to dig deeper into any of these “short list” drugs for 6B-001… and there might also be a few missing… I am hoping this draft article and these breadcrumbs are enough to fuel some more in-depth discussions in places such as reddit’s r/tinnitusresearch community, Tinnitus Talk (research section… also, shout out to My Posting Place crew), and…  our international friends in places such as MyTinnitus.de. (Speaking of which, if you run or manage a tinnitus forum that I have not yet linked to… and, your community discusses these newsletter issues and this website… feel free to send me an email and say hello. I always want to help people find places to discuss this research… and there’s a tinnitus forum out there for everyone.)

6B-001 Updates

If you would like to receive email updates regarding the development of 6B-001 for chronic tinnitus, subscribe to the Tinnitus Treatment Report email newsletter. It’s free, no spam, no third parties, your privacy is respected. It is an email newsletter that is sent 1-2 times per week. For anyone who wants to know about promising new tinnitus treatments (including experimental treatments and preclinical drugs such as 6B-001) — as early as possible… weeks, even months, before any other publication…

References

oliver twist please sir may i have a source meme

Yes, you may. More:

July 2021 update on Cognosetta’s tinnitus drug: CS0022

“These findings suggest that this pharmaceutical treatment may serve as a potential therapeutic in suppressing tinnitus symptoms.”

Reduction of Behavioral Manifestation of Tinnitus Through the Utilization of BK Channel Opener

Manisha Antony & Aarti Patel

Faculty Mentor: Joseph Walton (Department of Communication Sciences and Disorders)

Tinnitus, or “ringing in the ears”, is a prevalent hearing disorder. This study evaluates the effect of the drug candidate, CS0022, on the behavior of male CBA/CaJ mice with acoustic trauma (AT)-induced tinnitus. This compound is known to target the large-conductance calcium and voltage-activated potassium channel, or BK channel. This channel regulates neuronal excitability in the peripheral and central nervous system. Our hypothesis is that positive modulation of BK channel function mitigates changes in central auditory system activity that support the tinnitus percept. Behavioral evidence of tinnitus in mice models can be assessed through the quantification of the acoustic startle reflex and prepulse inhibition.

This study used Gap-Prepulse-Inhibition of the Acoustic Startle Response (GPIAS) to determine the presence and extent of tinnitus in the subjects. The GPIAS assay was first conducted on each mouse for baseline readings prior to AT with a 16 kHz narrowband noise. Post-AT behavioral assessments were conducted 7 to 9 weeks after trauma to select mice that developed tinnitus, while effect was assessed 10 to 11 weeks after trauma. Consecutively, Auditory Brainstem Responses (ABR) were collected to determine hearing thresholds of the subjects and helped evaluate the severity of threshold shifts. The findings suggest that treatment with CS0022 can improve AT-induced tinnitus in mice by modifying BK channels. The GPIAS results were statistically analyzed using a computational approach called Gstar. The ongoing analysis will focus on determining the relationship between the presence of tinnitus and the influence of treatment on permanent hearing loss.

Administration of BK Channel Agonist to Reduce Behavioral and Neural Manifestations of Tinnitus in Mice after Induced Acoustic Trauma

Kristie Labib & Malak Ibrahim

Faculty Mentor: Joseph Walton (Department of Communication Sciences and Disorders)

Tinnitus is a hearing disorder affecting approximately one third of all adults, and unfortunately has no FDA approved curative treatments. The deafferentation of central auditory structures as a result of ARHL or acoustic trauma (AT) causes a reduction in auditory sensory input. This then causes compensatory shifts in the balance of excitation and inhibition of the firing rate of the neurons within the CAS, which most often translates to hyperactivity. One particular BK channel modulator, known as CS0022, has been studied for its effect on hyper-excitability and inhibition in animal models. As a result, this study seeks to investigate this BK channel modulator therapy further and examine its effects on tinnitus in order to support its advancement and clinical usage. Auditory Steady State Responses (ASSRs) are electrophysiologic responses that display hearing sensitivity by evoking periodic amplitude-modulated tones (AM tones). They elicit steady state responses through neural phase-locking, which demonstrates auditory perceptive abilities. The study’s first objective is to examine the effects of AT on ASSR responses, as it is hypothesized that AT suppresses neural phase locking abilities. The study’s second objective is to examine the effect of CS0022 on the ASSRs of animals with AT-induced tinnitus, as it is hypothesized that CS0022 would enhance neural phase locking abilities. The data demonstrated that animals with tinnitus generally exhibited decreases in ASSR peak amplitudes following AT and increases in ASSR amplitudes following CS0022 administration. These findings suggest that this pharmaceutical treatment may serve as a potential therapeutic in suppressing tinnitus symptoms.

Meet the Researchers

This is from a June 2021 news article on the USFRI website’s newsroom:
https://www.usf.edu/research-innovation/news/2021/florida-corridor-students.aspx

MANISHA ANTONY

Research: Developing a novel therapeutic for treating tinnitus

Faculty Advisor: Professor Joseph Walton

Industry Partner: Cognosetta

Manisha Anthony recently graduated from USF with a degree in biomedical science and plans on attending medical school. She has been doing research at USF Professor Joseph Walton’s auditory neuroscience lab in the Department of Communication Science and Disorders for nearly two years. The lab focuses on studying tinnitus, a hearing disorder caused by age-related hearing loss or noise-induced trauma, and for which there are few effective treatments to lessen symptoms and no cure. She joined a project in Dr. Walton’s startup, Cognosetta, in 2020 that is working to develop a new drug to address tinnitus.

“Through my experience at Cognosetta, I was able to gain substantial knowledge that will help me with my future endeavors. I was able to be involved in various aspects of the research and the challenges I faced in this research has helped me be more independent and develop critical thinking skills. The most rewarding part for this experience was the wonderful opportunities for our team to present our accomplishments at the Undergraduate Research Conference and Association for Research in Otolaryngology. I am grateful to be a part of this research lab as it has opened an interest in neuroscience for me, which I hope to continue to study in the future. Most importantly I would like to thank my mentors Dr. Joseph Walton, Dr. Luisa Scott and Dr. Collin Park for guiding me and helping me achieve this honor.”

KRISTIE LABIB

Research: Developing a novel therapeutic for treating tinnitus

Faculty Advisor: Professor Joseph Walton

Industry Partner: Cognosetta

Kristie Labib recently graduated with a Bachelor of Science degree in biomedical sciences and will be starting at the USF Morsani College of Medicine in the fall of 2021. She also worked as an undergraduate in Dr. Walton’s lab on research projects on pharmaceutical and therapeutic methods at alleviating symptoms of tinnitus.

“My most valued experience in this research was my involvement in a project that examined the effectiveness of a new drug at suppressing symptoms of tinnitus. I was fortunate to work diligently on it with the support of my mentors Dr. Joseph Walton, Dr. Luisa Scott, and Dr. Collin Park. We observed successful results, which then drove me to write a USF Honors thesis on the neurological benefits of the drug on tinnitus symptoms. Additionally, we had the data presented on posters at both the Undergraduate Research Conference and the Association for Research in Otolaryngology. As part of the Cognosetta, Inc., team our work allowed us to be selected as one of the 21 Fibonacci Finalists in the Cade Prize research competition for Florida’s most innovative startups. Being able to share these achievements with my colleagues allowed us to grasp the impact we have on medicine through this project.
“I will forever be indebted to USF and my mentors, as this journey in tinnitus research fueled my desire to pursue a career in medicine. Although my experiences were unforgettable, I wish that this would only be the beginning of my journey, as I would like to pursue a career as an otolaryngologist after medical school.”

MALAK IBRAHIM

Research: Developing a novel therapeutic for treating tinnitus

Faculty Advisor: Professor Joseph Walton

Industry Partner: Cognosetta

Malak Ibrahim recently graduated from USF with a major in biomedical sciences and a minor in psychology. She will start at the Florida International University Herbert Wertheim College of Medicine in the fall. She conducted her undergraduate research on a potential pharmaceutical to treat tinnitus at USF’s Global Center for Hearing and Speech Research under Dr. Walton with the additional mentorship of Dr. Collin Park and Dr. Luisa Scott.

Malak conducted her USF Honors thesis work on the neurological testing used to evaluate a novel therapeutic theorized to alleviate the symptoms of tinnitus, as well as presented this research at USF’s 2021 Undergraduate Research Symposium. She hopes to continue conducting promising research as a future medical student and physician in order to advance medicine and healthcare.

“My years conducting research under Dr. Walton have proved to be an invaluable experience. I learned how to innovate and adapt in a professional, collaborative manner, skills that I am sure will aid me in my next step as a medical student. I also gained an appreciation for the medical applications of scientific exploration and how transformative they can be in healthcare.”

Updates

Get CS0022 updates through the Tinnitus Treatment Report email newsletter. It’s free and you get early access to “impossible”-to-find updates.

References

Simulated transient hearing loss improves auditory sensitivity

CATEGORY:
Research

TITLE:
Simulated transient hearing loss improves auditory sensitivity

DESCRIPTION:
Recently, it was proposed that a processing principle called adaptive stochastic resonance plays a major role in the auditory system, and serves to maintain optimal sensitivity even to highly variable sound pressure levels. As a side effect, in case of reduced auditory input, such as permanent hearing loss or frequency specific deprivation, this mechanism may eventually lead to the perception of phantom sounds like tinnitus or the Zwicker tone illusion. Using computational modeling, the…

CONTENT:
Sci Rep. 2021 Jul 20;11(1):14791. doi: 10.1038/s41598-021-94429-5.

ABSTRACT

Recently, it was proposed that a processing principle called adaptive stochastic resonance plays a major role in the auditory system, and serves to maintain optimal sensitivity even to highly variable sound pressure levels. As a side effect, in case of reduced auditory input, such as permanent hearing loss or frequency specific deprivation, this mechanism may eventually lead to the perception of phantom sounds like tinnitus or the Zwicker tone illusion. Using computational modeling, the biological plausibility of this processing principle was already demonstrated. Here, we provide experimental results that further support the stochastic resonance model of auditory perception. In particular, Mongolian gerbils were exposed to moderate intensity, non-damaging long-term notched noise, which mimics hearing loss for frequencies within the notch. Remarkably, the animals developed significantly increased sensitivity, i.e. improved hearing thresholds, for the frequency centered within the notch, but not for frequencies outside the notch. In addition, most animals treated with the new paradigm showed identical behavioral signs of phantom sound perception (tinnitus) as animals with acoustic trauma induced tinnitus. In contrast, animals treated with broadband noise as a control condition did not show any significant threshold change, nor behavioral signs of phantom sound perception.

PMID:34285327 | DOI:10.1038/s41598-021-94429-5

SOURCE:
Scientific reports

DATE – PUBLISHED:
2021-07-20T11:03:24Z

DATE – DOI: 2021-07-20T11:03:24Z
DATE – PUBMED: 2021 Jul 20
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 21 Jul 2021 06:00:00 -0400

DATE – RETRIEVED:
07/21/21 07:55AM
2021-07-21T07:55:41-04:00

IDENTIFIER:
pmid:34285327,doi:10.1038/s41598-021-94429-5

PUBMED ID:
pubmed:34285327

DOI:
10.1038/s41598-021-94429-5

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34285327/

LINK – DOI:
https://doi.org/10.1038/s41598-021-94429-5

LINK – PUBLISHER:
http://www.nature.com/articles/s41598-021-94429-5

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-07-21T07:55:41-04:00, www.tinnitustreatmentreport.com.

High Dose Oxytocin Nasal Spray for Treatment of Tinnitus

https://clinicaltrials.gov/ct2/show/NCT04210310?type=Intr&cond=Tinnitus&phase=012345&lupd_s=12%2F10%2F2019&lupd_d=14

Condition :   Tinnitus

Interventions :   Drug: Oxytocin;   Other: Placebo nasal spray

Sponsor :   NYU Langone Health

Not yet recruiting

High Dose Oxytocin Nasal Spray for Treatment of Tinnitus

NCT04210310

Tue, 24 Dec 2019 12:00:00 EST

Update: most recent record manually retrieved on August 3, 2020

Last Update Posted: January 30, 2020
Comments: Recruitment Status changed from “Not yet recruiting” to “Now recruiting”

Updated: July 12, 2021
Estimated primary completion date / completion date pushed back 12 months

Anti-Tinnitus Effects of “Prism Adaptation” Glasses: Researchers in France to Begin Major Study Next Month (August 2021)

New research project will investigate the therapeutic effects of a short exposure to prisms on hearing deficits of tinnitus.

Could special glasses offer relief to people with tinnitus? According to the science, it’s not such a crazy question…

anti-tinnitus prism glasses possible style?
Image Source / Credit: Stoelting Inc © Stoelting Co.

And a research project (led by Carine Michel) dedicated to finding out the answer has received a grant worth 213,408 euros (around $250,000 USD) from the ANR (France’s Agence Nationale De La Reserche).

Yes, the glasses may seem gimmicky, at first. But the science is fascinating…

From the official project description (emphasis ours):

Glasses to ear differently – GLAD

Our project aims at better understanding the link between visuo-motor plasticity (by using a short exposure to glasses shifting the visual field) and auditory perception to propose an innovative therapeutic method to reduce hearing loss. There are many evidences showing the therapeutic effects of prism adaptation on lateralized impairments, while our recent innovative result shows the effect of prism adaptation on auditory perception in healthy individuals (Michel et al., 2019; Bonnet et al., submitted).

Our project has two main objectives:

1) from a fundamental point of view, we will deepen our understanding of the effects of prism adaptation on auditory processes in healthy participants, and

2) from a clinical point of view, we will investigate the therapeutic effects of a short exposure to prisms on hearing deficits of tinnitus and presbycusis.

Importantly, this avenue of research builds on recent studies related to “visuo-motor plasticity” and something called “cross-modal enhancement”.

In short, the idea that tinkering with one sense (such as vision) can have an effect on another sense (such as hearing). And, hopefully, in a predictable way… that will allow such tinkering to perhaps someday serve as a volume knob for tinnitus. Or augment auditory perception by using the auditory’s connections to eyesight and visual areas of the brain (becoming well-established).

Some background and related research:

Modifying auditory perception with prisms? Aftereffects of prism adaptation on a wide auditory spectrum in musicians and nonmusicians
December 2020
https://www.sciencedirect.com/science/article/pii/S0001691820305436

Prism adaptation consists of pointing to visual targets while wearing prisms that shift the visual field laterally. The aftereffects are not restricted to sensorimotor level but extend to spatial cognition. There is a link between spatial representation and auditory frequency, with an association of low frequencies on the left side and high frequencies on the right side of space.

Influence of Visual Prism Adaptation on Auditory Space Representation
https://journals.sagepub.com/doi/full/10.1177/2041669517746701

We here show that there is indeed a slight influence of visual adaptation on the perceived direction of acoustic sources.

The research dollars appear to be attracted as well…

The Swiss National Science Foundation also recently funded a project related to audio-visual cross-modal effects: “Cross-modal interaction after brain lesion – the influence of auditory stimulation on visual neglect”. The project began earlier this year and will continue until February 2025.

From the project description (emphasis ours):

The relevance of our project is twofold. First, the project will shed light on the neuronal mechanisms underlying audio-visual cross-modal effects. Second, by clarifying how and to which degree audio-visual cross-modal effects may improve visuospatial attention in neglect patients, the project will potentially allow to develop new therapeutic approaches.

And if the connection to tinnitus still seems like a stretch… consider this paper from last year, “Increased risk of tinnitus in patients with early-onset cataracts: a nationwide population-based case-control study”, which concluded that “patients with early-onset cataract are at an increased risk of developing tinnitus in subsequent years”.

Note: that particular paper points to ROS (reactive oxygen species) as the main contributing factor… but it’s hard to ignore the eye-ear connection given the other emerging research and ongoing projects on the topic.

It gets the noggin’ joggin’:

Could a change in eyesight create a mismatch in auditory perception, and influence the central gain cause of tinnitus?

Hmmm…

It’s certainly a fair question.

Which might explain why some other big, familiar institutions are also investigating this vision-tinnitus axis.

For instance, this Johns Hopkins University project that began last July. Titled, “Cross-modal enhancement of auditory plasticity and performance in adults”, the project has received nearly $1 million USD in funding so far and will continue until June 2025, if everything goes as planned.

The project aims to discover the “mechanisms that can recover adult cortical plasticity is of essence to benefit recovery of hearing or for treating abnormal auditory processing as occurs with tinnitus.”

Here is the full project description — certainly worth a read (formatting and emphasis ours):

Cross-modal enhancement of auditory plasticity and performance in adults

It is well documented that the ability of the brain to undergo plasticity becomes limited in adults. In particular, sensory experience-dependent plasticity of cortical circuits is rather confined to a limited time during development, termed the critical period. Recovery and refinement of sensory processing is therefore difficult in adults. For example, the success rate of speech recognition in artificial cochlear implant patients becomes quite low, if the surgery is done later in life.

Hence discovery of mechanisms that can recover adult cortical plasticity is of essence to benefit recovery of hearing or for treating abnormal auditory processing as occurs with tinnitus.

We found that temporary visual deprivation is quite effective at producing large-scale plasticity in the adult primary auditory cortex (A1) of mice. Such changes occurred as potentiation of feedforward excitatory synapses from the primary auditory thalamus (MGBv) to layer 4 (L4) as well as L4 to L2/3. This was accompanied by weakening of synapses arising from lateral intracortical sources to L2/3 of A1. In parallel, we also observed refinement of cortical circuits of A1 L4 and L2/3. Collectively, these changes suggest that A1 circuit adapts to allow better processing of bottom-up auditory inputs, which is consistent with our published observation of refinement of A1 L4 neuronal receptive field and lowering of detection threshold in visually deprived mice. In this application, we aim to determine the mechanisms involved in driving adult A1 plasticity with visual deprivation, and whether visual deprivation improves auditory behavior in adults. Based on our observation that visual deprivation induced potentiation of thalamocortical (TC) inputs to A1 L4 requires audition, but no due to changes in the auditory environment, we surmise that there is central adaptation in circuits mediating auditory signals going through the thalamus and the cortex.

In particular, we hypothesize that short-term visual deprivation promotes A1 plasticity in adults by regulating inhibitory circuits at the level of thalamus and cortex (Aim 1). The circuit and synaptic adaptation seen in A1 following vision loss accompanied refinement of A1 L4 neural function, and is predicted to enhance auditory function.

We will examine how short- term visual deprivation alters auditory behavioral tasks in adults, and investigate whether this is due to changes in A1 neuronal responses and population encoding during auditory tasks using in vivo 2-photon imaging (Aim 2).

Results from our proposed study will provide mechanistic understanding on how short-term visual deprivation enables plasticity of adult A1 via regulation of thalamic and cortical circuits, and will provide means to enhance auditory processing in the adult brain that could benefit development of treatment options for enhancing or recovering auditory function as would be needed for better prognosis of artificial cochlear implants. Furthermore, our results can be generalized to provide insights into how cortical circuits adapt to losing major inputs as it may happen during injury, stroke, and neuronal degeneration.

Public Health Relevance

Discovering mechanisms to enhance adult brain function is of utmost importance when devising therapeutics to recover and refine normal brain function later in life. We found that temporarily depriving vision leads to recovery of plasticity in the adult auditory cortex, which can benefit auditory function. In this proposal, we aim to determine the mechanisms that allow recovery of adult brain plasticity, and whether temporary visual deprivation improves auditory performance in adults.

Interesting.

And perhaps even substantial enough to give those “gimmicky” glasses — which could potentially increase auditory perception (via multiple mechanisms)… and possibly alter or diminish tinnitus perception (to be determined) — some legitimacy. And in the context of all this research, perhaps this anti-tinnitus glasses project happening in France does not seem so “wacky” anymore…

But first, a quick rant:

Speaking of “wacky”, I have noticed an influx of Hope Police commenting on my articles and notes. “Hope Police” is the label I assign to people who feel the need to protect others from False Hope. They can be found commenting on articles like this one in Facebook groups or Reddit posts. They are easy to spot because they are Very Serious about making it clear that “THIS IS NOT THE TINNITUS CURE EVERYONE HAS BEEN WAITING FOR” and other variations of “NOTHING TO SEE HERE, KEEP IT MOVING.” In reality, what they really spread is False Nope. The opposite of False Hope and… a much bigger villain. Often these Hope Police and Protectors of Truth do not even bother reading the article. And so their criticisms are limited to the atmosphere of the article… what the article implied, apparently… or, get this… they explain how the problem with the article is that it could potentially be perceived by someone as suggesting the treatment in question is a cure. In other words, these Hope Police protect imaginary people from imaginary scenarios involving imaginary problems. Anyway, if you can’t already tell… it bugs me. But after giving it some more thought, I have decided to take the high road and… instead of publicly shaming these straw-treatment “debunkers”… I have decided to offer them a very special meme that will hopefully clear things up:

keep calm and realize this article does not claim these prism glasses are the tinnitus cure everyone has been waiting for
To: “Hope Police”
From: Love, Michael

That’s a peace offering.

As for everyone else…

I offer an invitation to join the newsletter (email updates)… that gives you “early access” to tinnitus treatment-related news and updates (that you won’t find anywhere else) — mostly pertaining to experimental not-yet-available tinnitus therapies. I send 1-2 issues per week. But only when something good is happening. See link below:

Updates

If you would like updates on the development of these “anti-tinnitus prism adaptation glasses” (as well as other experimental tinnitus-related treatments and not-yet-released drugs), subscribe to the email newsletter.

Last but not least, references for this [draft] article.

References

Impact of Sazetidine-A and Similar Nicotinic Drugs on Tinnitus

DRAFT COPY — you are seeing an “early access” version of this article. This report is sent to email newsletter subscribers, who receive it up to a week early.

Researchers at the Southern Illinois University School of Medicine have successfully tested a drug (sazetidine-A) related to the smoking cessation drug Chantix, in a sound-exposure animal model of tinnitus. Human clinical trials could begin as early as 2022…

This information is unclassified and from an Annual Progress Report prepared for the U.S. Army Medical Research and Development Command. From the report:

Tinnitus is the perception of sound in the absence of an environmental stimulus. This phantom sound in the head, is most commonly caused by noise exposure, resulting in damage to the inner ear. Within the veteran population seeking VA care, 16-27% suffer from serious hearing loss and tinnitus. Unfortunately, those most affected are bound to the sounds in their heads have difficulty concentrating, suffer from depression and may even contemplate suicide. We posit that breaking the bond between attention and tinnitus will ameliorate the impact of tinnitus. Drugs acting at receptors that bind the brain chemical acetylcholine (nAChRs), a substance involved in brain circuits that control attention could ameliorate tinnitus. We have successfully tested the drug (sazetidine-A), in an established sound-exposure animal model of tinnitus.

SOURCE: https://apps.dtic.mil/sti/pdfs/AD1114579.pdf

Preliminary studies are now starting to support their hypothesis: drugs that act at specific receptors that bind the brain chemical acetylcholine (nAChRs), a substance released by brain circuits that control attention, could alleviate tinnitus.

And these drugs, which include sazetidine-A (related to smoking cessation drug Chantix) and varenicline, could allow tinnitus sufferers with “habituation-proof” tinnitus to finally find relief thanks to a pill that — hypothetically — works to “disconnect” the looped circuit that may be preventing habituation (or extinguishment) from taking its normal course.

The result? Hopefully a way for people with severe disabling tinnitus to “get used to it” and have their tinnitus diminish, on its own, like most people… thanks to a drug involving the chemical substance involved in brain circuits that control attention. By addressing that chemically-based “habituation-proof” circuit, it could unlock the normalizing process.

Whether these drugs can do that remains to be proven. But the evidence from preliminary studies suggests it might be possible. That’s what this project is exploring.

From the progress report (which is dated August 2020 but only released publicly more recently):

4. Impact The results form SA1, delineated above, are the first of their kind to show significant tinnitus-related attentional abnormalities in principal AI output neurons. First they show significant abnormalities in the number and size of the presynaptic excitatory messages arriving at these neurons. Secondly they show significant tinnitus-related differences in nAChR sensitivity at different doses of acetylcholine. Since we will be pharmacologically targeting these receptors in attempts to normalize their tinnitus pathology, understanding these tinnitus-related differences is critical. The ability of sazetidine-A to effect disproportional changes in resting membrane potential and action potential threshold in animals with behavioral evidence of tinnitus suggests a unique receptor target. Finally, preliminary data suggests that sazetidine-A was able to normalize a tinnitus-related increased sensitivity to acetylcholine. Collectively, we feel these are exciting and highly publishable findings when matured. They also support the proposed SA2&3 studies.

The SA1, SA2, SA3 refer to “Specific Aims”, which are like goals/stages of the project. Right now, the researchers are in the final “stage” of this project. Human clinical trials would be a separate project that follows the completion of this one. I’m speculating, and I don’t know the future. But that’s where this is headed, as of now.

These findings and the theory behind these exciting hypotheses will continue to be studied and tested as part of this ongoing research project, “Nicotinic Receptor Pathology in Tinnitus: Auditory Cortex and Selective Desensitizing Nicotinic Agents” — which is supported by a grant of nearly $1.8 million, courtesy of the Department of Defense and the Congressionally Directed Medical Research Program.

Importantly, the research is aimed at treating the most severe cases of tinnitus: tinnitus that cannot be ignored or simply tuned out. Their goal is to develop new drugs capable of ameliorating tinnitus in “those most affected”, the people who are “bound to the sounds in their heads” and who “cannot do regular work”, “have great difficulty concentrating”, and “may even contemplate suicide”.

This is described in the project abstract (see below) along with more details about what is being studied and the hypothesis behind this new area of exploration in the realm of chronic tinnitus treatments.

As for the project itself… it is scheduled to complete in July 14, 2022 and… barring any surprises… it looks like human clinical trials could follow shortly after. Why so soon? Because the “new” drugs in question are closely related to already-approved smoking cessation drugs (such as Chantix)… in fact, Chantix might be a viable candidate, though we will have to wait and see to know for sure. In any case, the clinical trial process would likely be faster and less complex, as the safety profile of the drug is already well established in humans.

So it’s got that goin’ for it, which is nice.

Here are the details, including both abstracts (the second one is heavier on the science):

Nicotinic Receptor Pathology in Tinnitus: Auditory Cortex and Selective Desensitizing Nicotinic Agents

Principal Investigator: CASPARY, DONALD M
Institution Receiving Award: SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE
Program: PRMRP

PUBLIC ABSTRACT

Tinnitus is the perception of sound in the absence of an external environmental stimulus. This phantom sound in the head, sometimes referred to as “ringing in the ears,” is a Fiscal Year 2018 Peer Reviewed Medical Research Program topic area. It is most commonly caused by noise exposure, resulting in damage to the inner ear containing the hair cells and nerve fibers that carry sound to the brain. The military working environment presents many high noise situations with noise levels often so intense that standard hearing protection is not adequate. A recent study found that Soldiers deployed to battle zones were ~52 times more likely to suffer auditory damage than non-deployed Soldiers. The American Tinnitus Association reports that within the Veteran population seeking Department of Veterans Affairs (VA) care, 16%-27% suffer from serious hearing loss and tinnitus. The VA awarded disability compensation for serious hearing loss tinnitus to approximately 972,000 Veterans with an annual aggregate cost of nearly $1.5 billion. The U.S. Centers for Disease Control and Prevention estimates that more than 50 million Americans – nearly 15% of the population – experience some form of tinnitus, with 10%-15% of this total suffering extreme and debilitating tinnitus. Conversely, the majority of chronic tinnitus sufferers are able to ignore their tinnitus, tuning out the din while going about their daily lives. Unfortunately, those most affected are bound to the sounds in their heads; they have great difficulty concentrating, suffer from depression, cannot do regular work and may even contemplate suicide. Studies proposed here are focused on developing a treatment for those individuals most impacted by tinnitus. Our hypothesis postulates that breaking the bond between attention and tinnitus will ameliorate the impact of tinnitus, allowing patients to return to a more normal life. We propose that drugs that act at specific receptors that bind the brain chemical acetylcholine (nAChRs), a substance released by brain circuits that control attention could ameliorate tinnitus. Our preliminary studies have successfully tested a drug (sazetidine-A) related to the smoking cessation drug Chantix, in a sound-exposure animal model of tinnitus. All proposed studies will be carried out in our well-established rat tinnitus model, and our laboratories have significant experience in all proposed methods. Proposed studies will test the ability of Chantix to ameliorate tinnitus. Similar to what is seen in human tinnitus patients, our recent studies in a rat tinnitus model finds tinnitus-related deficits in selective attention. We will test if both these drugs related to nicotine can normalize selective attention in our animal model. Proposed basic science studies will test if these agents can normalize aberrant brain cell response properties recorded in structures located at the highest level of the central auditory system, the auditory cortex. Preliminary receptor binding studies suggest that nicotinic acetylcholine receptors are altered in animals with evidence of tinnitus. Proposed studies will map the markers for the different receptor subtypes that make up these acetylcholine receptors in animals with and without tinnitus. Using brain slices from auditory cortex of animals with and without tinnitus, proposed studies will examine the function and the pharmacology of these receptors and the impact of Chantix and similar nicotinic drugs on the response properties of these brain cells. Collectively, these studies will provide new pharmacologic information on possible novel treatments for tinnitus while improving our understanding of the relationship between attention and tinnitus suffering and the cellular mechanisms that underpin this hypothesis.

TECHNICAL ABSTRACT

Tinnitus is defined as a phantom sound (ringing in the ears) that can significantly affect the quality of life for those who suffer its effects. Noise exposure, with its consequent acoustic damage, is the most common cause of tinnitus. The military working environment presents many situational high noise levels, frequently so intense that standard hearing protection is inadequate. There is a growing awareness that maladaptive attentional mechanisms are involved in the pathology of tinnitus. Individuals most disturbed by their tinnitus have their attention bound to the percept while showing significantly impaired selective attention. Basal forebrain neurons involved in attentional circuits can increase release of the neuromodulator acetylcholine (ACh), where it acts at nicotinic cholinergic receptors (nAChRs), located on terminals and neurons in the primary auditory cortex (AI). This forebrain cholinergic system is a component of a perceptual network that may enhance attention to tinnitus as well as generating emotional reactions to tinnitus. The proposed basic science and translational studies will use a novel pharmacologic approach to treat individuals whose attention is inextricably bound to phantom sounds in their head. Our preliminary data indicate that the nAChR-Beta2 selective partial agonist and desensitizer sazetidine-A reduced the impact of tinnitus in our animal model. The focus of the present proposal is to examine the therapeutic potential of two nAChR partial agonists, sazetidine-A and the smoking cessation drug varenicline. Preliminary binding and subunit expression studies suggest that nAChR subunits are altered in AI of animals with behavioral evidence of tinnitus. All specific aims (SAs) will use an established sound-exposure rat model of tinnitus. SA1A will use immunoprecipitation and florescent in situ hybridization (FISH) to characterize tinnitus-related changes in heteromeric and homomeric nAChRs in AI neurons from animals with and without behavioral evidence of tinnitus. nAChRs comprising different combinations of subunits are present on presynaptic terminals/inputs that innervate neurons across layers of AI. Our preliminary studies show altered numbers and affinity of nAChRs in AI layers IV and VI. SA1B will characterize functional pharmacology of tinnitus-related changes in acetylcholine (ACh) evoked synaptic currents from AI layers IV and VI neurons in an AI slice preparation. SA1C will examine the pharmacologic responses of bath applied sazetidine-A and varenicline on ACh evoked synaptic currents from AI layer IV and VI neurons as in SA1B. SA2A will catalog and compare tinnitus-related changes in AI single-unit responses from awake animals with and without behavioral evidence of tinnitus, while attempting to normalize tinnitus-related aberrant unit responses with systemic injections of sazetidine-A and varenicline. SA3A will test whether varenicline, similar to sazetidine-A, can ameliorate tinnitus in our animal model. SA3B is based on findings that animals with behavioral evidence of tinnitus, similar to human tinnitus sufferers, show impaired selective auditory attention. Others have shown that sazetidine-A can normalize impaired visual attention. SA3B will examine the ability of sazetidine-A and varenicline to normalize impaired selective attention in animals with behavioral evidence of tinnitus. Collectively, results from these proposed studies will directly test the hypothesis that tinnitus can be ameliorated using attention-altering drugs while examining basic science mechanisms underpinning this hypothesis at the level of the auditory cortex.

That’s all for now.

This article is a DRAFT and you are receiving early access because you are subscribed to email updates (or the link was shared by someone who is subscribed). How to get updates:

Updates

I will be releasing more updates and progress reports on this project, as they become available, leading up to July 14, 2022. Sign up for the TinnitusTreatmentReport.com newsletter to get these articles (it’s free and I send updates that do not appear on the front page of this website). I am not involved in the study and I do not have any information about human trials!

References

Review of Pharmacotherapy for Tinnitus

CATEGORY:
Research

TITLE:
Review of Pharmacotherapy for Tinnitus

DESCRIPTION:
Various medications are currently used in the treatment of tinnitus, including anesthetics, antiarrhythmics, anticonvulsants, antidepressants, antihistamines, antipsychotics, anxiolytics, calcium channel blockers, cholinergic antagonists, NMDA antagonists, muscle relaxants, vasodilators, and vitamins. To date, however, no medications have been specifically approved to treat tinnitus by the US Food and Drug Administration (FDA). In addition, medicines used to treat other diseases, as well as…

CONTENT:
Healthcare (Basel). 2021 Jun 21;9(6):779. doi: 10.3390/healthcare9060779.

ABSTRACT

Various medications are currently used in the treatment of tinnitus, including anesthetics, antiarrhythmics, anticonvulsants, antidepressants, antihistamines, antipsychotics, anxiolytics, calcium channel blockers, cholinergic antagonists, NMDA antagonists, muscle relaxants, vasodilators, and vitamins. To date, however, no medications have been specifically approved to treat tinnitus by the US Food and Drug Administration (FDA). In addition, medicines used to treat other diseases, as well as foods and other ingested materials, can result in unwanted tinnitus. These include alcohol, antineoplastic chemotherapeutic agents and heavy metals, antimetabolites, antitumor agents, antibiotics, caffeine, cocaine, marijuana, nonnarcotic analgesics and antipyretics, ototoxic antibiotics and diuretics, oral contraceptives, quinine and chloroquine, and salicylates. This review, therefore, describes the medications currently used to treat tinnitus, including their mechanisms of action, therapeutic effects, dosages, and side-effects. In addition, this review describes the medications, foods, and other ingested agents that can induce unwanted tinnitus, as well as their mechanisms of action.

PMID:34205776 | DOI:10.3390/healthcare9060779

SOURCE:
Healthcare (Basel, Switzerland)

DATE – PUBLISHED:
2021-06-21T18:24:05Z

DATE – DOI: 2021-06-21T18:24:05Z
DATE – PUBMED: 2021 Jun 21
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 02 Jul 2021 06:00:00 -0400

DATE – RETRIEVED:
07/02/21 07:26AM
2021-07-02T07:26:00-04:00

IDENTIFIER:
pmid:34205776,doi:10.3390/healthcare9060779

PUBMED ID:
pubmed:34205776

DOI:
10.3390/healthcare9060779

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34205776/

LINK – DOI:
https://doi.org/10.3390/healthcare9060779

LINK – PUBLISHER:
https://www.mdpi.com/2227-9032/9/6/779

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-07-02T07:26:00-04:00, www.tinnitustreatmentreport.com.

Sulodexide Anticoagulant Therapy for Chronic Tinnitus: Phase 3 Clinical Trials — When?

American Tinnitus Association sulodexide article screenshot

An important update on the development status of sulodexide, an anticoagulant drug that significantly reduced tinnitus severity scores in a phase 2 clinical trial in patients with chronic subjective tinnitus.

Background:

Sulodexide is a “highly purified mixture of glycosaminoglycans composed of low molecular weight heparin (80%) and dermatan sulfate (20%).”

It successfully completed a phase 2 study, “Randomized Double Blind Controlled Trial on Sulodexide Efficacy in Chronic Idiopathic Subjective Tinnitus”, and the results have already been published.

Quick summary:

  • Sulodexide decreased tinnitus severity in patients with chronic subjective tinnitus. The results were statistically significant and sulodexide outperformed the placebo. It also reduced tinnitus regardless of whether someone started the treatment with severe tinnitus or mild tinnitus.
  • The trial was randomized, double-blinded, and included a placebo group. The results demonstrated that people who received sulodexide experienced greater decreases in their tinnitus scores compared to people who only received a placebo.
  • The treatment regimen involved taking 2 oral tablets each day (one in the morning, one in the evening) for 40 consecutive days. Half the group received the real sulodexide tablets and the other half received placebo tablets.

Journal article sulodexide sagepub screenshot

What happened AFTER the results were published…

These phase 2 results were first published a little over three years ago, on May 1, 2018, in a paper titled, “Sulodexide Monotherapy in Chronic Idiopathic Subjective Tinnitus: A Randomized Controlled Trial” and… the results were so impressive, the American Tinnitus Association wrote glowingly about sulodexide in that year’s Summer issue of Tinnitus Today, their flagship publication. From the article, “Anticoagulant Sulodexide Therapy for Tinnitus”:

After the 40-day administration of placebo or sulodexide, a significantly lower THI score was found in the group that had taken sulodexide, compared to those taking placebo (THI score of 30.1 and 40.5, respectively). Scores on the Mini-TQ also demonstrated a greater decrease for those taking sulodexide (average of 9.7 vs. 12.5). Further analysis showed that those taking sulodexide demonstrated decreased scores on the THI and Mini-TQ, regardless of their beginning score. The mechanisms by which sulodexide may improve tinnitus are not yet understood. However, this study demonstrated that this drug has potential to reduce the severity of tinnitus and holds promise for further study in this area.

Since then, sulodexide continues to be mentioned in a growing number of scientific papers. Most recently, the study of sulodexide was cited in a paper from April 16, 2021, titled, “Methodological Aspects of Randomized Controlled Trials for Tinnitus: A Systematic Review and How a Decision Support System Could Overcome Barriers”, published in the Journal of Clinical Medicine.

Another paper, also published within the last 12 months, titled “Auditory Neural Plasticity in Tinnitus Mechanisms and Management”, described how certain mechanisms behind sulodexide are connected to tinnitus:

There are also reports of drugs that can improve the microcirculation of the cochlea by improving the blood flow and thus increasing the clearance of ROS through the bloodstream […] and sulodexide has antithrombotic and anticoagulant activities, both of which have been shown to have positive effects in tinnitus patients […] mainly by improving the subjective perception and emotional response to tinnitus. However, the changes of inner ear microcirculation in tinnitus are not completely clear yet, and various antioxidants still need to pass through the blood-labyrinth barrier; thus, the therapeutic effect is not very precise.

Meanwhile, further recognition of its therapeutic potential (emphasis: potential) can be found in other credible sources, too. For example, in a 28-page clinical policy bulletin from health care giant, Aetna, on the topic of tinnitus treatments. Within that document, sulodexide — “a natural glycosaminoglycan with anti-thrombotic, profibrinolytic and vascular anti-inflammatory properties” — is categorized as an experimental and investigational tinnitus treatment option and the bulletin mentions how researchers believe sulodexide holds promise.

And yet…

Here is what is happening right now:

Sulodexide is currently “stuck” between phase 2 and phase 3 clinical trials.

And nothing has happened for the last three years. Its advancement toward a potential approval for use in chronic tinnitus has been frozen.

But unlike other promising treatments that seem to mysteriously “vanish”… and which receive a lot of attention and fanfare… only to “ghost” the tinnitus community without explanation…

The reason sulodexide “ghosted” actually has nothing to do with a clinical trial failure, retraction of results, some scary side effect that was later discovered, patent issues, lawsuits… nor does it have anything to do with some Big Pharma conspiracy to withhold a possible tinnitus treatment because it’s not profitable enough.

The reality of the situation is much more complex. But also simple to explain:

The geopolitical situation in the country where sulodexide was being studied and where the clinical trials took place (and conceivably, would have continued to take place) is not able to support its further advancement into phase 3 at this time.

I am going to respect the privacy of the individuals I contacted while investigating the situation here…

But that’s the situation.

To reiterate: there exists, at this very moment, a phase 3-worthy tinnitus treatment (a drug) that seems to hold great promise… and it is NOT moving forwarad — at all.

It is “stranded” in between phase 2 and phase 3.

It has been so for years. Nothing has happened, with respect to its advancement toward phase 3 and perhaps some day an approval, since the end of the last phase 2.

I know that might be sad to read for some people.

But the good news is, there is no “expiry date” and it can be unfrozen, unstuck, unpaused, and…

Unforgotten.

The only danger is for the community and research community to “forget” about sulodexide (or any other promising candidate, for that matter).

That appears to be what has happened. Consider this: big budget marketing campaigns and savvy PR departments exist to make sure you don’t forget about FX-322, Lenire, etc. But there is nobody actively working to make sure sulodexide receives your attention and driving its advancement and funding.

Whether that changes will ultimately be up to you — the community — and the organizations and people who are in a position that allows them to make the necessary arrangements required to give sulodexide (and the people who study it) a chance at continuing the next leg of this valuable work.

My hope is that this article can get the process started and put sulodexide back on the radar. (Side note: A few people on TinnitusTalk did notice, back in 2018. But that, sadly, was not enough. The thread, for whatever reason, did not grab the attention of the rest of the community at the time, and became inactive.)

The community — which means YOU — can decide whether it is worth discussing. Worth emailing organizations asking them for their position on this treatment. Talking about it on reddit, TinnitusTalk, Facebook, wherever else.

See what happens.

How to get updates on this situation:

Please remember to sign up for the TinnitusTreatmentReport.com email newsletter for ongoing updates about sulodexide and other promising tinnitus drug candidates.

References

https://journals.sagepub.com/doi/10.1177/0194599818767618

https://clinicaltrials.gov/ct2/show/NCT02737670

https://www.aetnabetterhealth.com/pennsylvania/assets/pdf/provider/guidelines/medical/Medical/Tinnitus-Treatments.pdf

https://www.mdpi.com/2077-0383/10/8/1737

https://www.hindawi.com/journals/np/2020/7438461/

https://en.wikipedia.org/wiki/Sulodexide

https://www.tinnitustalk.com/threads/sulodexide-possibly-benefits-chronic-tinnitus.17918/

https://clinicaltrials.gov/ct2/show/NCT02737670

OTO-313 in Subjects With Unilateral Subjective Tinnitus

CATEGORY:
Clinical Trials

TITLE:
OTO-313 in Subjects With Unilateral Subjective Tinnitus

DESCRIPTION:
Condition :   Subjective Tinnitus

Interventions :   Drug: OTO-313;   Drug: Placebo

Sponsor :   Otonomy, Inc.

Recruiting

GUID:
NCT04829214

ID:
NCT04829214

DATE – FIRST POSTED:
Fri, 02 Apr 2021 12:00:00 EDT

DATE – LAST UPDATED:
04/02/21 06:57AM

DATE – RETRIEVED:
04/02/21 06:57AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04829214?type=Intr&cond=Tinnitus&phase=012345&lupd_s=04%2F01%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04829214

Insufficient Evidence: Gabapentin’s Efficacy in Tinnitus Treatment – A Systematic Review

CATEGORY:
Research

TITLE:
Analysis of Gabapentin’s Efficacy in Tinnitus Treatment: A Systematic Review

DESCRIPTION:
CONCLUSIONS: There is insufficient evidence to recommend the use of gabapentin for patients with tinnitus.

CONTENT:
Ann Otol Rhinol Laryngol. 2021 May 26:34894211018921. doi: 10.1177/00034894211018921. Online ahead of print.

ABSTRACT

OBJECTIVES: Tinnitus can be a chronic symptom that brings disability and distress. Some studies suggested that gabapentin might be effective on tinnitus relief. The objective of the study is to perform a systematic review in order to evaluate the efficacy of oral gabapentin in patients with tinnitus.

METHODS: A literature search was conducted in English and following the recommendations from PRISMA. The terms used were: (“tinnitus” OR “subjective tinnitus”) AND (“gabapentin”). The study selection was performed following the eligibility criteria in accordance to the PICOS (population, intervention, comparison, outcome, study design) strategy-patients with tinnitus; oral gabapentin; placebo; reduction of tinnitus severity questionnaires scores; prospective, double-blind, randomized controlled trial, respectively. The selected studies were included in qualitative synthesis. The studies were analyzed according to Joanna Briggs Institute’s critical appraisal checklist for randomized controlled trials.

RESULTS: One hundred twenty-one studies were found in 9 databases and 8 studies were found in gray literature. After study selection, 6 articles were read in full. Then, 2 studies were excluded and 4 were included in qualitative synthesis. All 4 articles were analyzed according to critical evaluation checklist.

CONCLUSIONS: There is insufficient evidence to recommend the use of gabapentin for patients with tinnitus.

PMID:34036823 | DOI:10.1177/00034894211018921

SOURCE:
The Annals of otology, rhinology, and laryngology

DATE – PUBLISHED:
2021-05-26T09:16:22Z

DATE – DOI: 2021-05-26T09:16:22Z
DATE – PUBMED: 2021 May 26
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 26 May 2021 06:00:00 -0400

DATE – RETRIEVED:
05/26/21 06:30PM
2021-05-26T18:30:49-04:00

IDENTIFIER:
pmid:34036823,doi:10.1177/00034894211018921

PUBMED ID:
pubmed:34036823

DOI:
10.1177/00034894211018921

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34036823/

LINK – DOI:
https://doi.org/10.1177/00034894211018921

LINK – PUBLISHER:
http://journals.sagepub.com/doi/10.1177/00034894211018921

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-05-26T18:30:49-04:00, www.tinnitustreatmentreport.com.

Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus

https://clinicaltrials.gov/ct2/show/NCT03336398?type=Intr&cond=Tinnitus&phase=012345&lupd_s=09%2F15%2F2020&lupd_d=14

Condition :   Tinnitus

Interventions :   Drug: Ketamine Hydrochloride in saline;   Drug: Saline

Sponsor :   New York State Psychiatric Institute

Recruiting

Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus

NCT03336398

Wed, 08 Nov 2017 12:00:00 EST

Last Update Posted:

09/29/20 06:51AM

New Research from Susan Shore Explores Connections Between Tinnitus, Hyperacusis, and Signal Processing in Noisy Environments

Very short update:

A new Susan Shore research paper was just posted online.

It is a preprint (not-yet-peer-reviewed) and was added to bioRxiv a few days ago on May 21, 2021.

The title of the paper is, “Cochlear nucleus small cells use olivocochlear collaterals to encode sounds in noise”. The authors are Susan E. Shore, Calvin Wu, Adam Hockley.

Here is the abstract:

Abstract

Understanding speech, especially in noisy environments, is crucial to social interactions. Yet, as we age, speech processing can be disrupted by cochlear damage and the subsequent auditory nerve fiber degeneration. The most vulnerable-medium and high-threshold-auditory nerve fibers innervate various cell types in the cochlear nucleus, among which, the small cells are unique in receiving this input exclusively. Here, we characterize small cell firing characteristics, demonstrating superior temporal as well as intensity coding. We show that small-cell unique coding properties are facilitated by direct cholinergic input from the medial olivocochlear system. These results highlight the small cell-olivocochlear circuit as a key player in signal processing in noisy environments, which may be selectively degraded in aging or after noise insult.

Here is a link to the full text version (PDF):

https://www.biorxiv.org/content/10.1101/2021.05.20.444983v1.full.pdf

As you probably noticed, the word “tinnitus” is not mentioned up front. Nowhere in title, nowhere in abstract.

But it does appear deeper in the text. As does the word “hyperacusis”, another connection here.

new shore paper screenshot with word tinnitus and hyperacusis

This post is just a quick share. I have not had time to go through the paper and analyze its findings. I only learned about it within the past hour.

But from what I have seen so far, the connections to tinnitus and hyperacusis that Shore references here are quite interesting. And they become more clear once we take a look at the research she cites.

Here is a link to that paper, “Increased contralateral suppression of otoacoustic emissions indicates a hyperresponsive medial olivocochlear system in humans with tinnitus and hyperacusis”:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269714/

That’s all for now. Because it is 12:58 AM here in Montreal, Quebec and I just wanted to share this brand new Susan Shore research preprint update with you before going to bed.

The source of this information:

Like most of the research I post and highlight, this preprint appeared on my radar thanks to the fully automated system that monitors, collects, filters, and organizes the research papers listed on TinnitusTreatmentReport.com. This system runs 24/7 and specifically tracks tinnitus-related research (and news, and clinical trials, and…) from a fairly long list of sources – one of which is bioRxiv, the biology preprint server hosted down at the Cold Spring Harbor Laboratory.

This meme captures the essence of how this system helps me keep up with freshly posted Susan Shore research:

Susan Shore research appeared meme

Goodnight.

This update is for Tinnitus Treatment Report email subscribers. If you are reading this but have not yet subscribed — you can join the email updates list here. It’s free. There is no spam. No promotional emails. And your information is kept private. Expect between 1-3 emails per week (but only the good stuff).

Role of microRNA‑375‑3p‑mediated regulation in tinnitus development

https://www.spandidos-publications.com/10.3892/ijmm.2021.4969

https://pubmed.ncbi.nlm.nih.gov/34036397/

Role of microRNA‑375‑3p‑mediated regulation in tinnitus development

Abstract

Changes in the dorsal cochlear nucleus (DCN) following exposure to noise play an important role in the development of tinnitus. As the development of several diseases is known to be associated with microRNAs (miRNAs/miRs), the aim of the present study was to identify the miRNAs that may be implicated in pathogenic changes in the DCN, resulting in tinnitus. A previously developed tinnitus animal model was used for this study. The study consisted of four stages, including identification of candidate miRNAs involved in tinnitus development using miRNA microarray analysis, validation of miRNA expression using reverse transcription‑quantitative PCR (RT‑qPCR), evaluation of the effects of candidate miRNA overexpression on tinnitus development through injection of a candidate miRNA mimic or mimic negative control, and target prediction of candidate miRNAs using mRNA microarray analysis and western blotting. The miRNA microarray and RT‑qPCR analyses revealed that miR‑375‑3p expression was significantly reduced in the tinnitus group compared with that in the non‑tinnitus group. Additionally, miR‑375‑3p overexpression via injection of miR‑375‑3p mimic reduced the proportion of animals with persistent tinnitus. Based on mRNA microarray and western blot analyses, connective tissue growth factor (CTGF) was identified as a potential target for miR‑375‑3p. Thus, it was inferred that CTGF downregulation by miR‑375‑3p may weaken with the decrease in miRNA expression, and the increased pro‑apoptotic activity of CTGF may result in more severe neuronal damage, contributing to tinnitus development. These findings are expected to contribute significantly to the development of a novel therapeutic approach to tinnitus, thereby bringing about a significant breakthrough in the treatment of this potentially debilitating condition.

Cochlear nucleus small cells use olivocochlear collaterals to encode sounds in noise [Preprint] [Susan Shore]

https://www.biorxiv.org/content/10.1101/2021.05.20.444983v1

https://www.biorxiv.org/content/10.1101/2021.05.20.444983v1.full.pdf

Cochlear nucleus small cells use olivocochlear collaterals to encode sounds in noise
Adam Hockley, Calvin Wu, Susan E Shore
doi: https://doi.org/10.1101/2021.05.20.444983

Abstract
Understanding speech, especially in noisy environments, is crucial to social interactions. Yet, as we age, speech processing can be disrupted by cochlear damage and the subsequent auditory nerve fiber degeneration. The most vulnerable-medium and high-threshold-auditory nerve fibers innervate various cell types in the cochlear nucleus, among which, the small cells are unique in receiving this input exclusively. Here, we characterize small cell firing characteristics, demonstrating superior temporal as well as intensity coding. We show that small-cell unique coding properties are facilitated by direct cholinergic input from the medial olivocochlear system. These results highlight the small cell-olivocochlear circuit as a key player in signal processing in noisy environments, which may be selectively degraded in aging or after noise insult.

Pre-emptive MOC-pathway enhancement protects the cochlea from synaptopathic acoustic
304 trauma (Boero et al., 2018), but whether increased MOC activation following synaptopathic noise
305 exposure could reverse speech-in-noise deficits is still unknown. Conversely, in humans with
306 tinnitus or hyperacusis, an increased contralateral suppression of otoacoustic emissions
307 (Knudson et al., 2014) suggests an over-responsive MOC system in this pathology. MOC neurons
308 are modulated by descending input from the inferior colliculus (Malmierca et al., 1996; Robertson
309 & Mulders, 2000; Schofield & Cant, 1999), auditory cortex (Coomes & Schofield, 2004; Mulders
310 & Robertson, 2000), and local inhibitory interneurons of the medial nucleus of the trapezoid body
311 (Torres Cadenas et al., 2020). Descending modulation may be a route for auditory attention to
312 affect peripheral processing, which may explain attentional facilitation of speech-in-noise
313 understanding (de Boer et al., 2012). Descending modulation of MOC activity would also affect
available under aCC-BY-NC-ND 4.0 International license.
was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.20.444983; this version posted May 21, 2021. The copyright holder for this preprint (which
13
314 MOC collateral input to CN SCs, which accurately encode intensity, providing an additional action
315 pathway for auditory attention. The SCC in humans occupies a larger proportion of the CN than
316 in rodents, and is therefore poised to play a major role in central mechanisms of speech
317 perception (Moore & Osen, 1979).

Efficacy of donepezil in patients with chronic tinnitus

Researchers in Brazil are studying the effects of donepezil in patients with chronic tinnitus.

Some quick details on donepezil and the new phase 2 trial:

Donepezil is a drug that is similar to memantine, rivastigmine, and galantamine.

From Wikipedia:

Donepezil was approved for medical use in the United States in 1996. It is available as a generic medication. In 2018, it was the 128th most commonly prescribed medication in the United States, with more than 5 million prescriptions.

It is a cholinesterase inhibitor that “inhibits voltage-activated sodium currents reversibly and delays rectifier potassium currents and fast transient potassium currents.” More detailed information available here: https://www.ncbi.nlm.nih.gov/books/NBK513257/

It is already approved and used to treat other conditions (such as Alzheimer’s disease) – though its effects are apparently small and its mechanism still not fully understood.

And now it is being investigated as part of a phase 2 trial to determine whether or not it can help people with chronic tinnitus caused by sensorineural hearing loss.

The study was registered about 6 months ago on November 3, 2020.

It will enroll up to 50 participants.

According to the study record, the date of first enrollment = January 29, 2021.

But according to that same study record, the study status = Not yet recruiting.

Which means there was probably either a delay in starting the trial or a delay in updating parts of the study record. (Probably the latter.)

This information is current as of May 17, 2021. However, it is based on records that are only current as of February 23, 2021. So, the current status might actually be recruiting. We just can’t tell from the current study record.

But it does tell us about outcomes and the hypothesis:

Primary Outcome(s)
Improvement is expected from patients with tinnitus who will use the medication comparing to placebo group. The methods Student’s t test and ANOVA analysis will be used, before and after placebo and active drug therapy, for quantitative variables. Statistical significance level of 0.05 or 5% will be adopted for two-tailed samples and study power of 95%. The qualitative variables will be described by their frequency of presentation.

Secondary Outcome(s)
The memory improvement is expected from patients who will use the medication comparing to placebo group. The methods Student’s t test and ANOVA analysis will be used, before and after placebo and active drug therapy, for quantitative variables. Statistical significance level of 0.05 or 5% will be adopted for two-tailed samples and study power of 95%. The qualitative variables will be described by their frequency of presentation.

That’s all for now.

This article is a PREVIEW COPY [draft]. As a subscriber to TinnitusTreatmentReport.com email updates, you get access to it a few days early – before it is posted to the front page.

Not signed up? Subscribe here. It’s free and you can expect between 1-3 emails per week (but only if something is happening). No spam, no promotional emails, privacy respected.

References

Further reading

Important Reminder

  • nothing on this website qualifies as medical advice and is not intended to guide treatment decisions
  • everything you read or see here is for entertainment or informational purposes only
  • do not attempt to “copy” this trial’s intervention or try a “do-it-yourself” regimen
  • donepezil can have extremely serious side effects for some people (including withdrawal effects)
  • always talk to a doctor or qualified professional when making treatment decisions
  • have a nice day

Ketamine + HD-tIPNS for tinnitus: Professor Dirk De Ridder investigates effects of new “drug/device combo” therapy

Professor Dirk De Ridder, a world-leading expert in tinnitus, is investigating the combined effect of ketamine and brain stimulation on tinnitus loudness and distress, as part of a new phase 1/2 clinical trial.

The aim of the study is to determine if low dose ketamine, through its effects on brain plasticity, is able to catalyze transcranial electrical stimulation, and reduce tinnitus severity as a result.

Starstim 32 neuroelectric headset for ketamine tinnitus trial
Behold… The Starstim 32 headset (device) that will be used alongside ketamine (drug), for this device/drug combination therapy trial.

A total of 24 participants with chronic tinnitus will get a chance to receive treatment with the experimental drug/device combination therapy, at the University of Otago Dunedin School of Medicine, in New Zealand. The treatment will be delivered twice, 10 days apart.

ketamine molecule
Ketamine molecule. Not quite as cool-looking as the headset device. But still, an essential part of the combo therapy.

Inclusion criteria: Adults aged between 18-70 years with constant subjective tinnitus and a grade of 3 or higher (considered “moderate to severe”) on the tinnitus questionnaire.

The trial (Registration number: ACTRN12621000119897p), titled “Effect of ketamine and concomitant multi-target high definition transcranial electrical stimulation on tinnitus loudness and distress in adults- A feasibility and safety study”, is registered prospectively on the Australia New Zealand Clinical Trials Registry.

Ketamine device/drug combination therapy trial for tinnitus screenshot

As of May 12, 2021, it is unclear whether or not anyone has been enrolled (yet) or if the coordinators have begun recruiting participants.

The anticipated date of first enrollment is listed as February 15, 2021. However, according to the provisional study record, the trial’s ethics application is still awaiting approval.

Here is some more information, taken directly from the provisional study record (emphasis/formatting ours):

Ketamine and High Definition, Trancranial Infraslow Pink Noise Stimulation (HD-tIPNS)

The intervention arm will receive a low dose of subcutaneous ketamine (0.5mg/kg) as a bolus, from a clinician experienced in administration. This will be followed by HD-tIPNS administered for a single session of 30 minutes duration, beginning ~25 minutes after ketamine delivery, by a researcher experienced in administering neuromodulation techniques.

A battery-driven wireless 32 channel transcranial current stimulator (Starstim32 TCS®, Neuroelectrics) will be used to deliver stimulation while the participants are comfortably and quietly seated. Simulation [sic] is delivered by AgCl electrodes placed in the international 10-20 arrangement, secured in a neoprene cap (see Neuroelectrics website for headset image). For the active treatment group, the stimulation will be delivered at a current strength of maximum of 2mA for 30min, with 60s ramp up and ramp down at the beginning and end of each stimulation session, with continuous stimulation in between. For sham stimulation, to create an identical skin sensation to the active stimulation, the current will be applied for a 60s ramp up (0-2mA) and 60s ramp down (2-0mA) at the beginning and the end of each stimulation session, without any current for the remainder of the stimulation period.

This Intervention will be delivered twice, spaced 10 days apart. Intervention duration will be a total of 2 hours in length to allow for safety monitoring. After a 20 day washout, both groups will transition to the intervention, delivered twice again, 10 days apart.

The delayed start occurs as follows: Participants can be allocated to start with Ketamine + Active Stimulation or Ketamine + Sham Stimulation. Both the sham stimulation and the active stimulation groups will receive active stimulation after the 20 day washout (the Ketamine + Sham stimulation is the active control). Therefore the Ketamine + Sham stimulation (Active control) receives a delay to the start of active intervention.

Participants will undergo treatment at the Department of Psychological medicine laboratory at the Dunedin School of Medicine, University of Otago.

  • Intervention [1] Treatment: Drugs
  • Intervention [2] Treatment: Devices

Comparator / control treatment: Participants in the control arm will receive a low dose of subcutaneous ketamine (0.5mg/kg) as a bolus, from a clinician experienced in administration. This will be followed by Sham stimulation, designed to create identical skin sensations to active stimulation. Participants will use identical equipment to that of the active group, and will receive a short dose of the treatment protocol, mimicking the initial tingling/prickling commonly experienced with Transcranial electrical stimulation.

Primary outcome
Tinnitus Functional Index (TFI). The TFI has eight subscales that address the intrusiveness of tinnitus, the sense of control the patient has, cognitive interference, sleep disturbance, auditory issues, relaxation issues, quality of life, and emotional distress. This provides an overall measure of how much of a problem tinnitus is for participants (severity).

  • Adults aged between 18-70 years with constant subjective tinnitus and a grade of 3 or above on the tinnitus questionnaire.
  • Minimum age 18 Years
  • Maximum age 70 Years
  • Gender Both males and females

This article will be updated as more information is added to the study record.

For additional updates related to this ketamine/brain stimulation combination therapy (and other experimental not-yet-available tinnitus treatments), subscribe to the Tinnitus Treatment Report newsletter (email updates). It’s free, there’s no spam or sneaky promotional emails, and your information is kept private.

References

Questions? Comments? Feedback? Send an email to michael@urgentresearch.com and say hello.

Evaluation of the OtoBand as a Treatment to Reduce the Perceived Loudness of Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Evaluation of the OtoBand as a Treatment to Reduce the Perceived Loudness of Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Interventions :   Device: Otoband;   Device: Placebo

Sponsor :   Otolith Labs

Recruiting

GUID:
NCT04787653

ID:
NCT04787653

DATE – FIRST POSTED:
Mon, 08 Mar 2021 12:00:00 EST

DATE – LAST UPDATED:
03/08/21 06:05AM

DATE – RETRIEVED:
03/08/21 06:05AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04787653?type=Intr&cond=Tinnitus&phase=012345&lupd_s=03%2F07%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04787653

Cell-based approach for increasing central auditory inhibition

Project Number
5F30DC018185-03

Contact PI/Project Leader
OWOC, MARYANNA

Awardee Organization
UNIVERSITY OF PITTSBURGH AT PITTSBURGH

Description

Abstract

Project Summary/Abstract: Multiple lines of evidence suggest that acoustic overexposure results in cochlear damage and decreased inhibition in auditory centers, contributing to deficits in temporal processing, tinnitus, and hyperacusis. Previous attempts to correct this hyper-excitable state have focused on increasing GABAergic inhibitory tone systemically, with some success in providing tinnitus relief. However, the side effect profile of these drugs impose constraints on the dose, duration, and safety of use. A more precise treatment that locally increases inhibition in auditory nuclei could potentially treat the underlying pathology while minimizing off-target side effects. The inferior colliculus (IC), a major subcortical integration center of the central auditory pathway, is a particularly apt target to explore the effects of local increases in inhibition, as it plays an important role in mediating some acoustic behaviors (such as gap detection and pre-pulse inhibition) and demonstrates hyper- excitable response properties following acoustic overexposure. A potential approach to increase inhibition locally in the IC is through transplantation of cells from the medial ganglionic eminence (MGE), the birthplace of eventual cortical inhibitory interneurons. While naturally destined for the cerebral cortex, transplanted MGE cells have been shown to survive, integrate, and increase the number of inhibitory events in non-cortical circuits, such as the spinal cord. As a first step toward understanding the potential role local increases in inhibition may have in mitigating the effects of acoustic exposure, I propose to test the hypothesis that transplanted MGE cells will functionally integrate into IC circuits in adult CBA/CaJ mice, mitigating the reduced inhibition seen in noise exposed subjects. Three specific aims are proposed: 1) Characterize the migration and differentiation of MGE cells transplanted into the IC of naïve and noise exposed mice. 2) Determine how transplantation of MGE cells affects auditory behavior in adult CBA/CaJ mice. 3) Determine the effects of MGE cell transplantation on spontaneous and sound-evoked responses of IC neurons in vivo. These experiments represent a novel application of MGE cell transplantation and will improve our understanding of the pathological inhibition that might underlie the formation and persistence of auditory pathologies such as tinnitus and hyperacusis, and in the long run may lead to the development of novel treatment strategies.

Public Health Relevance Statement

Project Narrative: Acoustic overexposure not only increases hearing thresholds but can result in complex auditory pathologies that can have a detrimental effect on quality of life and account for a major source of financial burden. Current treatment options for deficits resulting from acoustic overexposure provide symptomatic relief in select cases but are often inadequate and are limited by the fact that the underlying neural mechanisms are not well understood. The proposed studies will investigate how local changes in the excitatory/inhibitory balance in the inferior colliculus, a critical site of auditory processing in the midbrain, may contribute to the formation and persistence of auditory pathologies, such as tinnitus and hyperacusis, and in the long run may lead to the development of novel treatment strategies.

Project Funding for FY 2021
$51,036

Cochlear Promontory Stimulation for Treatment of Tinnitus

https://clinicaltrials.gov/ct2/show/NCT03759834?type=Intr&cond=Tinnitus&phase=012345&lupd_s=11%2F16%2F2018&lupd_d=14

Condition :   Tinnitus

Intervention :   Device: Cochlear promontory stimulation

Sponsor :   Mayo Clinic

Active, not recruiting

Cochlear Promontory Stimulation for Treatment of Tinnitus

NCT03759834

Fri, 30 Nov 2018 12:00:00 EST

>>> https://clinicaltrials.gov/ProvidedDocs/34/NCT03759834/ICF_000.pdf

University of Granada researchers identify genes linked to severe tinnitus

https://www.audiology-worldnews.com/research/4082-university-of-granada-researchers-identify-genes-linked-to-tinnitus

Studying tinnitus linked to different disorders can lead to the identification of molecular mechanisms, early diagnosis, and the application of new drugs for treating tinnitus.

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00102-X/fulltext

University of Granada researchers identify genes linked to tinnitus

Added value of this study

We have found a significant enrichment of missense rare variants in synaptic genes including ANK2, TSC2 and AKAP9 in patients with tinnitus extreme phenotype in Meniere disease patients. We also replicated these findings in an independent cohort of tinnitus patients from Sweden. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, the top GO terms being membrane trafficking and cytoskeletal protein binding in neurons.

This is the first study reporting the association of rare variation in ANK2, TSC2 and, AKAP9 genes with severe tinnitus and supports the involvement of membrane trafficking and cytoskeletal protein binding in the pathophysiology of severe tinnitus.

An fMRI Investigation of the Effects of IV Lidocaine on Tinnitus

CATEGORY:
Clinical Trials

TITLE:
An fMRI Investigation of the Effects of IV Lidocaine on Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Intervention :   Drug: IV Lidocaine

Sponsor :   Massachusetts Eye and Ear Infirmary

Recruiting

GUID:
NCT04192773

ID:
NCT04192773

DATE – FIRST POSTED:
Tue, 10 Dec 2019 12:00:00 EST

DATE – LAST UPDATED:
04/29/21 06:19AM

DATE – RETRIEVED:
04/29/21 06:19AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04192773?type=Intr&cond=Tinnitus&phase=012345&lupd_s=04%2F28%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04192773

UPDATE: Status changed to Recruiting

Investigating Disinhibitory Brain Mechanism in Tinnitus and Hearing Loss [Diagnostic]

CATEGORY:
Clinical Trials

TITLE:
Investigating Disinhibitory Brain Mechanism in Tinnitus and Hearing Loss

DESCRIPTION:
Conditions :   Tinnitus;   Hearing Loss

Intervention :   Other: MRI scanning

Sponsors :   University of Nottingham;   Nottingham University Hospitals NHS Trust

Not yet recruiting

GUID:
NCT04862572

ID:
NCT04862572

DATE – FIRST POSTED:
Wed, 28 Apr 2021 12:00:00 EDT

DATE – LAST UPDATED:
04/28/21 07:41AM

DATE – RETRIEVED:
04/28/21 07:41AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04862572?type=Intr&cond=Tinnitus&phase=012345&lupd_s=04%2F27%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04862572

Researchers evaluating the effects of bitter almond oil and cinnarizine on chronic tinnitus severity

A new phase 3 clinical trial for tinnitus has begun recruiting at Mazandaran University of Medical Sciences, a top medical university in Iran.

Researchers will investigate whether or not a combination of bitter almond oil and cinnarizine can reduce tinnitus severity in patients with chronic tinnitus.

The title of the study is “The Efficacy of bitter almond oil on the severity of chronic tinnitus.”

Iran bitter almond oil tinnitus study
This study was found “hiding” on a little-known Iranian clinical trial registry. We verified it by cross-referencing the study’s unique registration identifiers in a WHO database as well as the Cochrane Central Register of Clinical Trials.

Participants in the treatment group will receive a combination of bitter almond ear drops and cinnarizine tablets, twice daily (every 12 hours), for one month.

Tinnitus severity will be measured thrice three times: 1) immediately before treatment begins, 2) after two weeks of treatment, and 3) after 4 weeks of treatment, using VAS and THI scores.

This trial was registered on February 16, 2021 and will enroll up to 70 patients with doctor-confirmed chronic tinnitus, between the ages of 17 and 75, male and/or female.

As of March 1, 2021, recruiting for this study was set to begin on March 5, 2021. No reason to assume that date has changed. But we will update this post as we get more information.

As for the treatment itself – a unique combination of ear drops and tablets – here is some very basic background information:

More information on bitter almond oil will follow. For now, an important warning:

WARNING: “bitter almond oil” might sound like a harmless natural ingredient, but in reality it is associated with some extremely serious chemical compounds (i.e. cyanide). Needless to say, there is NO safe (or legal) do-it-yourself approach to copying this trial. Or any trial, for that matter… but especially this trial.

Some interesting information on the cinnarizine component, from the Meniere’s Society UK:

Cinnarizine has two pharmacological actions. It is a calcium antagonist, though not a powerful one. This acts mainly on the blood vessels and prevents constriction on these vessels. In theory it therefore improves the micro circulation of the ear. At the same time it has a mild antihistaminic effect.

Remember to subscribe to the email newsletter for updates related to this cinnarizine/bitter almond combination therapy (and news about other experimental tinnitus treatments in development).

References

The bewitched ear: State of the art genomics research on tinnitus

CATEGORY:
Research

TITLE:
The bewitched ear: State of the art genomics research on tinnitus

DESCRIPTION:
No abstract

CONTENT:
EBioMedicine. 2021 Apr 24;67:103349. doi: 10.1016/j.ebiom.2021.103349. Online ahead of print.

NO ABSTRACT

PMID:33906065 | DOI:10.1016/j.ebiom.2021.103349

SOURCE:
EBioMedicine

DATE – PUBLISHED:
2021-04-25T03:17:37Z

DATE – DOI: 2021-04-25T03:17:37Z
DATE – PUBMED: 2021 Apr 24
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 27 Apr 2021 06:00:00 -0400

DATE – RETRIEVED:
04/28/21 06:25AM
2021-04-28T06:25:10-04:00

IDENTIFIER:
pmid:33906065,doi:10.1016/j.ebiom.2021.103349

PUBMED ID:
pubmed:33906065

DOI:
10.1016/j.ebiom.2021.103349

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33906065/

LINK – DOI:
https://doi.org/10.1016/j.ebiom.2021.103349

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S2352396421001420

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00142-0/fulltext

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-04-28T06:25:10-04:00, www.tinnitustreatmentreport.com.

Otonomy Now Recruiting Participants for Phase 2 Study of OTO-313 in Tinnitus [Update: New Locations Added]

Otonomy’s recently announced OTO-313 clinical trial was posted to ClinicalTrials.gov on April 2 and will enroll an estimated 140 participants.

Here is a link to the official study record (NCT03918109): A Randomized, Double-blind, Placebo-controlled Phase 2 Study of OTO-313 Given as a Single Intratympanic Injection in Subjects With Unilateral Subjective Tinnitus

OTO-313 Recruiting April 2, 2021Status: Recruiting

April 11 Update: As we predicted, the OTO-313 study has now expanded its study locations and is currently recruiting in seven states: California, Colorado, Florida, Louisiana, North Carolina, South Carolina, and Utah. (We expected all these locations, with the one surprise being South Carolina.)

The new OTO-313 study is currently recruiting in two locations: Florida and North Carolina.

However, we expect to see more recruitment sites added across the United States in the coming weeks.

Here are some likely states the trial will expand to (based on the previous OTO-313 study locations): California, Colorado, Illinois, Kentucky, Louisiana, New Jersey, New York, North Carolina, Texas, Utah, West Virginia.

International expansion?

It is unknown whether this phase of the trial will expand to other countries.

More updates to follow…

Remember to subscribe to the email newsletter for upcoming OTO-313 updates (and news about other experimental tinnitus treatments in development).

Activity of CaMKIIa+ dorsal cochlear nucleus neurons are crucial for tinnitus perception but not for tinnitus induction [Preprint]

https://www.biorxiv.org/content/10.1101/2021.04.06.438667v1.full

Activity of CaMKIIa+ dorsal cochlear nucleus neurons are crucial for tinnitus perception but not for tinnitus induction

https://doi.org/10.1101/2021.04.06.438667

Abstract

The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca2+/Calmodulin kinase 2α (CaMKIIα) positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus. Mice were exposed to loud noise (9-11kHz, 90dBSPL, 1h, followed by 2h of silence) and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded two days before and two weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKIIα+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKIIα+ DCN units decrease tinnitus-like responses (p = 0.038, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKIIα-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKIIα-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise exposure (n = 6 experimental and 6 control mice). Our results suggest that CaMKIIα-hM4Di positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.

Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study

CATEGORY:
Research

TITLE:
Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study

DESCRIPTION:
BACKGROUND: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe…

CONTENT:
EBioMedicine. 2021 Apr 1;66:103309. doi: 10.1016/j.ebiom.2021.103309. Online ahead of print.

ABSTRACT

BACKGROUND: tinnitus is a heterogeneous condition associated with audiological and/or mental disorders. Chronic, severe tinnitus is reported in 1% of the population and it shows a relevant heritability, according to twins, adoptees and familial aggregation studies. The genetic contribution to severe tinnitus is unknown since large genomic studies include individuals with self-reported tinnitus and large heterogeneity in the phenotype. The aim of this study was to identify genes for severe tinnitus in patients with extreme phenotype.

METHODS: for this extreme phenotype study, we used three different cohorts with European ancestry (Spanish with Meniere disease (MD), Swedes tinnitus and European generalized epilepsy). In addition, four independent control datasets were also used for comparisons. Whole-exome sequencing was performed for the MD and epilepsy cohorts and whole-genome sequencing was carried out in Swedes with tinnitus.

FINDINGS: we found an enrichment of rare missense variants in 24 synaptic genes in a Spanish cohort, the most significant being PRUNE2, AKAP9, SORBS1, ITGAX, ANK2, KIF20B and TSC2 (p < 2E-04 ), when they were compared with reference datasets. This burden was replicated for ANK2 gene in a Swedish cohort with 97 tinnitus individuals, and in a subset of 34 Swedish patients with severe tinnitus for ANK2, AKAP9 and TSC2 genes (p < 2E-02 ). However, these associations were not significant in a third cohort of 701 generalized epilepsy individuals without tinnitus. Gene ontology (GO) and gene-set enrichment analyses revealed several pathways and biological processes involved in severe tinnitus, including membrane trafficking and cytoskeletal protein binding in neurons. INTERPRETATION: a burden of rare variants in ANK2, AKAP9 and TSC2 is associated with severe tinnitus. ANK2, encodes a cytoskeleton scaffolding protein that coordinates the assembly of several proteins, drives axonal branching and influences connectivity in neurons. PMID:33813136 | DOI:10.1016/j.ebiom.2021.103309 SOURCE: EBioMedicine DATE - PUBLISHED: 2021-04-02T07:03:04Z DATE - DOI: 2021-04-02T07:03:04Z DATE - PUBMED: 2021 Apr 1 DATE OUTPUT MATCHED: True DATE - ADDED: Sun, 04 Apr 2021 06:00:00 -0400 DATE - RETRIEVED: 04/05/21 01:42AM 2021-04-05T01:42:04-04:00 IDENTIFIER: pmid:33813136,doi:10.1016/j.ebiom.2021.103309 PUBMED ID: pubmed:33813136 DOI: 10.1016/j.ebiom.2021.103309 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33813136/ LINK - DOI: https://doi.org/10.1016/j.ebiom.2021.103309 LINK - PUBLISHER: https://linkinghub.elsevier.com/retrieve/pii/S235239642100102X REFERENCES: Tinnitus Treatment Report, Urgent Research, 2021-04-05T01:42:04-04:00, www.tinnitustreatmentreport.com.

What’s the Buzz? The Neuroscience and the Treatment of Tinnitus [Thanos Tzounopoulos]

CATEGORY:
Research

TITLE:
What’s the Buzz? The Neuroscience and the Treatment of Tinnitus

DESCRIPTION:
Tinnitus is a pervasive public health issue that affects approximately 15% of the United States population. Similar estimates have also been shown on a global scale, with similar prevalence found in Europe, Asia, and Africa. The severity of tinnitus is heterogeneous, ranging from mildly bothersome to extremely disruptive. In the United States, approximately 10-20% of individuals who experience tinnitus report symptoms that severely reduce their quality of life. Due to the huge personal and…

CONTENT:
Physiol Rev. 2021 Mar 26. doi: 10.1152/physrev.00029.2020. Online ahead of print.

ABSTRACT

Tinnitus is a pervasive public health issue that affects approximately 15% of the United States population. Similar estimates have also been shown on a global scale, with similar prevalence found in Europe, Asia, and Africa. The severity of tinnitus is heterogeneous, ranging from mildly bothersome to extremely disruptive. In the United States, approximately 10-20% of individuals who experience tinnitus report symptoms that severely reduce their quality of life. Due to the huge personal and societal burden, in the last twenty years a concerted effort on basic and clinical research has significantly advanced our understanding and treatment of this disorder. Yet, neither full understanding, nor cure exists. We know that tinnitus is the persistent involuntary phantom percept of internally-generated non-verbal noises and tones, which in most cases is initiated, by acquired hearing loss and maintained only when this loss is coupled with distinct neuronal changes in auditory and extra-auditory brain networks. Yet, the exact mechanisms and patterns of neural activity that are necessary and sufficient for the perceptual generation and maintenance of tinnitus remain incompletely understood. Combinations of animal model and human research will be essential in filling these gaps. Nevertheless, the existing progress in investigating the neurophysiological mechanisms has improved current treatment and highlighted novel targets for drug development and clinical trials. The aim of this review is to thoroughly discuss the current state of human and animal tinnitus research, outline current challenges, and highlight new and exciting research opportunities.

PMID:33769102 | DOI:10.1152/physrev.00029.2020

SOURCE:
Physiological reviews

DATE – PUBLISHED:
2021-03-26T13:02:58Z

DATE – DOI: 2021-03-26T13:02:58Z
DATE – PUBMED: 2021 Mar 26
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 26 Mar 2021 06:00:00 -0400

DATE – RETRIEVED:
03/26/21 03:50PM
2021-03-26T15:50:44-04:00

IDENTIFIER:
pmid:33769102,doi:10.1152/physrev.00029.2020

PUBMED ID:
pubmed:33769102

DOI:
10.1152/physrev.00029.2020

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33769102/

LINK – DOI:
https://doi.org/10.1152/physrev.00029.2020

LINK – PUBLISHER:
https://journals.physiology.org/doi/10.1152/physrev.00029.2020

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-03-26T15:50:44-04:00, www.tinnitustreatmentreport.com.

Otonomy Initiates Phase 2 Clinical Trial of OTO-313 in Tinnitus

https://investors.otonomy.com/news-releases/news-release-details/otonomy-initiates-phase-2-clinical-trial-oto-313-tinnitus

Otonomy Initiates Phase 2 Clinical Trial of OTO-313 in Tinnitus
March 25, 2021 at 7:30 AM EDT
Phase 2 study design based on successful Phase 1/2 trial including use of Tinnitus Functional Index (TFI) responder analysis for primary efficacy endpoint
Patient enrollment criteria refined to enrich study population
Top-line results expected in mid-2022

MISSING: Day-90 Study Results on Impact of FX-322 on Tinnitus…

FX-322 tinnitus missing milk carton memeNotably absent from the recent FX-322 data readout: partial data on measures of FX-322 on tinnitus.

In fact, there is no mention of “tinnitus” at all.

None.

What’s going on?

Dear Frequency Therapeutics,

We understand that the timing and completeness of data readouts is subject to change. Such is the nature of forward looking statements.

But when things do change – things such as the availability of FX-322 day-90 tinnitus-related data – you ought to mention it.

Consider this:

Your clinical trials include tinnitus-related outcomes as a secondary outcome measure…

Your previous press releases mention tinnitus…

Your corporate presentations and event slides mention tinnitus.

In January, you listed “partial data on measures of FX-322 on tinnitus” as part of the anticipated phase 2a readout (planned for late Q1 2021)…

And yet, two days ago, on March 23, you released an update that did not even include the word “tinnitus” in the text.

Not even in the tiny text at the bottom. (We looked everywhere.)

Why not?

Until Frequency Therapeutics releases a statement or formal update on tinnitus study results, it is reasonable to assume there is no good news. There seems to be no other explanation as to why the word tinnitus was “scrubbed” from the ongoing list of talking points.

skeptical cat meme fx-322

Prove us wrong, Frequency Therapeutics.

Because we hope we’re wrong. We hope there’s promising tinnitus data somewhere that someone forgot to publish or mention. But, sadly, that seems unlikely.

To our readers: as soon as we have more information about FX-322 and tinnitus… we will be sending it out via the email newsletter. But it’s important to remember that FX-322 is NOT the only “horse in the race” toward effective tinnitus treatments. Others exist. And we will be posting information about them next week. (Note: these treatments have received far less mainstream attention and PR than “famous” upcoming drugs such as FX-322… yet some are surprisingly further along in their development than you might expect.)

Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

CATEGORY:
Research

TITLE:
Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

DESCRIPTION:
Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable…

CONTENT:
Sci Rep. 2021 Mar 19;11(1):6470. doi: 10.1038/s41598-021-85871-6.

ABSTRACT

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case-control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E-08), rs4900545 (p = 1.8E-08) and 14:103042287_CT_C (p = 3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E-06. PMID:33742053 | DOI:10.1038/s41598-021-85871-6 SOURCE: Scientific reports DATE - PUBLISHED: 2021-03-19T13:06:54Z DATE - DOI: 2021-03-19T13:06:54Z DATE - PUBMED: 2021 Mar 19 DATE OUTPUT MATCHED: True DATE - ADDED: Sat, 20 Mar 2021 06:00:00 -0400 DATE - RETRIEVED: 03/20/21 05:25PM 2021-03-20T17:25:35-04:00 IDENTIFIER: pmid:33742053,doi:10.1038/s41598-021-85871-6 PUBMED ID: pubmed:33742053 DOI: 10.1038/s41598-021-85871-6 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33742053/ LINK - DOI: https://doi.org/10.1038/s41598-021-85871-6 LINK - PUBLISHER: http://www.nature.com/articles/s41598-021-85871-6 REFERENCES: Tinnitus Treatment Report, Urgent Research, 2021-03-20T17:25:35-04:00, www.tinnitustreatmentreport.com.

Effect of Highly Bioavailable Curcumin on Subjective Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Effect of Highly Bioavailable Curcumin on Subjective Tinnitus

DESCRIPTION:
Condition :   Tinnitus, Subjective

Interventions :   Biological: Curcumin-phosphatidylcholine;   Biological: Placebo capsule

Sponsor :   Ascension South East Michigan

Recruiting

GUID:
NCT04800107

ID:
NCT04800107

DATE – FIRST POSTED:
Tue, 16 Mar 2021 12:00:00 EDT

DATE – LAST UPDATED:
03/16/21 09:56AM

DATE – RETRIEVED:
03/16/21 09:56AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04800107?type=Intr&cond=Tinnitus&phase=012345&lupd_s=03%2F15%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04800107

Effectiveness of Intratympanic Dexamethasone With Lignocaine for Alleviation of Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Effectiveness of Intratympanic Dexamethasone With Ligmocaine for Alleviation of Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Intervention :   Drug: Dexamethasone

Sponsor :   Combined Military Hospital, Pakistan

Active, not recruiting

GUID:
NCT04798391

ID:
NCT04798391

DATE – FIRST POSTED:
Mon, 15 Mar 2021 12:00:00 EDT

DATE – LAST UPDATED:
03/15/21 10:41AM

DATE – RETRIEVED:
03/15/21 10:41AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT04798391?type=Intr&cond=Tinnitus&phase=012345&lupd_s=03%2F14%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04798391

Otolith Labs Initiates Clinical Trial of OtoBand Device as a Treatment to Reduce Perceived Loudness of Tinnitus

A new clinical trial from Otolith Labs, a U.S. Defense Department-backed startup developing a device that could potentially extinguish the debilitating symptoms of vertigo, motion sickness, and now… lower tinnitus volume?

Otolith Labs Logo
Otolith Labs logo. Source: Otolith Labs (https://otolithlabs.com)

The study, titled Evaluation of the OtoBand as a Treatment to Reduce the Perceived Loudness of Tinnitus (NCT04787653) was posted to ClinicalTrials.gov on March 8, 2021 (a few hours ago, as of this writing).

Placebo-controlled study…

Unlike the Neuromod (Lenire) clinical trials, this OtoBand study involves a placebo device and group. (We here at Tinnitus Treatment Report applaud this decision.)

OtoBand study record screenshot
Here is a screenshot of the OtoBand clinical trial record… which was added to ClinicalTrials.gov *today* (March 8, 2021)

Here is a brief summary of how the study – which is an at-home study (conducted remotely and does not require travel to/from the clinic) – will work:

This proposed study is a blinded study in which the participant will wear the OtoBand when their tinnitus is present to determine if the OtoBand reduces the perceived loudness of their tinnitus. The Study will be placebo controlled with each participant using an effective device for half of the enrollment period and a placebo device for half of the enrollment period. The order of placebo and effective usage will be randomized, and the researchers will be blinded to which device a participant is using. Study participants will be instructed in an online telehealth conference on how to operate the OtoBand and how to wear the OtoBand. Participants will be enrolled for approximately 30 days from Informed Consent to Wrap-up call.

Great, but what does this “OtoBand device” look like?

Here is a photo from Otolith Labs company website:

Otoband Device Tinnitus
Source: Otolith Labs (https://otolithlabs.com)

We are unsure if this is the *exact* same model of the Otoband device that is being studied for its potential in reducing tinnitus loudness. The above photo might be an earlier version, a prototype. Plus, we do not know what design changes might be made during development. (It is not uncommon to see the design of novel devices like this evolve over time.)

As for the effectiveness of the device… we do not know anything yet. That’s what this clinical trial will hopefully tell us, in time…

Are we there yet are we there yet how about now? meme tinnitus treatment

Otoband clinical trial results… available when?

Not sure yet. The study was literally only added to the ClinicalTrials.gov database today. Too early to even guess. But here’s a good way to stay current with what’s happening:

For updates on the progress of OtoBand, I invite you to sign up for the Tinnitus Treatment Report email newsletter. It’s an easy way to get the very latest in tinnitus treatment development news and updates. For devices such as OtoBand, as well as pharmacological updates (e.g., FX-322, OTO-313, CS0022, and more). The email updates are 100% free and – importantly – your information is never shared with third parties, and you an unsubscribe with one click. Simple.

The first issue will begin sending soon (perhaps an exclusive update related to FX-322’s upcoming tinnitus study results)…

Got feedback? Send an email to michael@urgentresearch.com and speak your mind. Request an update!

Effectiveness of photobiomodulation in the management of tinnitus remains debatable: A systematic review

CATEGORY:
Research

TITLE:
Efficacy of photobiomodulation in the management of tinnitus: A systematic review of randomized control trials

DESCRIPTION:
There is a controversy in regards to the efficacy of photobiomodulation (PBM) in the management of tinnitus. The aim was to systematically review randomized controlled trials (RCTs) that assessed the efficacy of PBM (low-level laser therapy) in the management of tinnitus. The focused question was “Is PBM effective in the management of tinnitus?”. Indexed databases were searched up to and including June 2020 using different combinations of the following key words: (a) laser; (b) diode; (c)…

CONTENT:
Eur Ann Otorhinolaryngol Head Neck Dis. 2021 Mar 5:S1879-7296(21)00043-0. doi: 10.1016/j.anorl.2020.10.013. Online ahead of print.

ABSTRACT

There is a controversy in regards to the efficacy of photobiomodulation (PBM) in the management of tinnitus. The aim was to systematically review randomized controlled trials (RCTs) that assessed the efficacy of PBM (low-level laser therapy) in the management of tinnitus. The focused question was “Is PBM effective in the management of tinnitus?”. Indexed databases were searched up to and including June 2020 using different combinations of the following key words: (a) laser; (b) diode; (c) low-level laser therapy; (d) photobiomodulation; (e) tinnitus; (f) medium-level laser; (g) photo-biomodulation; and (h) low-power laser; and RCTs performed on humans were included. Letters to the editor; case reports/series; commentaries; experimental studies and historic reviews were excluded. The risk of bias was assessed using the modified cochrane collaboration tool. The format of the current systematic review was personalized to summarize the appropriate information. Ten RCTs (2 single-blinded and 8 double-blinded) were included. One study reported 30% and 100% resolution of tinnitus using diode and Neodymium-doped Yttrium Aluminum Garnet lasers; respectively. One study reported that PBM was effective in relieving tinnitus for up to 3 months. Eight studies reported that PBM was ineffective in the management of chronic tinnitus. The risk of bias was high; medium and low in 4; 5 and 1 studies; respectively. The effectiveness of PBM in the management of tinnitus remains debatable. Further power-adjusted and well-designed RCTs with long-term follow-up are needed.

PMID:33685826 | DOI:10.1016/j.anorl.2020.10.013

SOURCE:
European annals of otorhinolaryngology, head and neck diseases

DATE – PUBLISHED:
2021-03-07T15:51:15Z

DATE – DOI: 2021-03-07T15:51:15Z
DATE – PUBMED: 2021 Mar 5
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 09 Mar 2021 06:00:00 -0500

DATE – RETRIEVED:
03/09/21 07:23AM
2021-03-09T07:23:35-05:00

IDENTIFIER:
pmid:33685826,doi:10.1016/j.anorl.2020.10.013

PUBMED ID:
pubmed:33685826

DOI:
10.1016/j.anorl.2020.10.013

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33685826/

LINK – DOI:
https://doi.org/10.1016/j.anorl.2020.10.013

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1879729621000430

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-03-09T07:23:35-05:00, www.tinnitustreatmentreport.com.

Increased Serum Lipid Levels in Patients with Subjective Tinnitus

CATEGORY:
Research

TITLE:
Increased Serum Lipid Levels in Patients with Subjective Tinnitus

DESCRIPTION:
CONCLUSION: The results indicated that TC, TRG and LDL levels were significantly higher in tinnitus group and this increase implicates the potential role of hyperlipidemia associated with altered lipid metabolism in the etiology of tinnitus. We suggest that serum lipid levels could be useful and conducive in the diagnosis and prognosis of tinnitus.

CONTENT:
Iran J Otorhinolaryngol. 2021 Jan;33(114):31-36. doi: 10.22038/ijorl.2020.43663.2442.

ABSTRACT

INTRODUCTION: The aim was to investigate the link between tinnitus and serum levels of total cholesterol (TC), triglyceride (TRG), low-density (LDL) and high-density lipoprotein (HDL) in the central anatolian Turkish population.

MATERIALS AND METHODS: The retrospective and case-control study included a total of 91 patients with subjective tinnitus and a control group of age- and sex-matched 65 healthy volunteers. A detailed otolaryngologic examination followed by pure tone audiometry, serum lipid values, and magnetic resonance imaging of the temporal bone was performed. The clinical characteristics of tinnitus were registered for all patients. The serum levels of TC, TRG, LDL and HDL were compared between the two groups.

RESULTS: Mean TC level was 200.57±41.06 mg/dL in the patient group and 179.0±39.03 mg/dL in the control group (P=0.001). Mean TRG level was 177.76±86.94 mg/dL in the patient group and 124.43±61.44 mg/dL in the control group (P=0.000). Mean LDL level was 115.88±32.56 mg/dL in the patient group and 101.31±34.42 mg/dL in the control group (P=0.008). Mean HDL level was 50.25±13.60 mg/dL in the patient group and 53.46±12.66 mg/dL in the control group (P=0.137). Among all the serum lipids, TC, TRG and LDL established a significant difference between the two groups.

CONCLUSION: The results indicated that TC, TRG and LDL levels were significantly higher in tinnitus group and this increase implicates the potential role of hyperlipidemia associated with altered lipid metabolism in the etiology of tinnitus. We suggest that serum lipid levels could be useful and conducive in the diagnosis and prognosis of tinnitus.

PMID:33654688 | PMC:PMC7897436 | DOI:10.22038/ijorl.2020.43663.2442

SOURCE:
Iranian journal of otorhinolaryngology

DATE – PUBLISHED:
2021-02-21T23:07:27Z

DATE – DOI: 2021-02-21T23:07:27Z
DATE – PUBMED:
DATE OUTPUT MATCHED: False

DATE – ADDED:
Wed, 03 Mar 2021 06:00:00 -0500

DATE – RETRIEVED:
03/03/21 08:03AM
2021-03-03T08:03:01-05:00

IDENTIFIER:
pmid:33654688,pmc:PMC7897436,doi:10.22038/ijorl.2020.43663.2442

PUBMED ID:
pubmed:33654688

DOI:
10.22038/ijorl.2020.43663.2442

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33654688/

LINK – DOI:
https://doi.org/10.22038/ijorl.2020.43663.2442

LINK – PUBLISHER:
https://ijorl.mums.ac.ir/article_17205.html

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-03-03T08:03:01-05:00, www.tinnitustreatmentreport.com.

The progression of chronic tinnitus over the years

CATEGORY:
Research

TITLE:
The progression of chronic tinnitus over the years

DESCRIPTION:
Little is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were…

CONTENT:
Sci Rep. 2021 Feb 18;11(1):4162. doi: 10.1038/s41598-021-83068-5.

ABSTRACT

Little is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were associated to changes in tinnitus distress over time. Data from 388 patients with chronic tinnitus who visited a tertiary tinnitus clinic between 2012 and 2017 were interrogated via a mail survey in 2018. Tinnitus characteristics were measured with the Tinnitus Sample Case History Questionnaire and numeric rating scales; tinnitus distress with Tinnitus Handicap Inventory (THI) and the Tinnitus Questionnaire (TQ), depression with the Major Depression Inventory and Quality of life with the World Health Organisation Quality of Life BREF at both time points and the clinical global impression scale. Comorbidities experienced and undertaken treatments were assessed with an in-house survey. Three participants (0.8% of the sample) reported tinnitus remission between both assessments. A decrease in the THI and TQ, and numeric ratings for tinnitus severity, annoyance, unpleasantness, and discomfort was observed, but no differences in tinnitus characteristics, depression, quality of life or overall health status. 64% presented at least one comorbidity, and 88% sought at least on tinnitus-specific treatment. Common comorbidities were psychological and sleeping problems, and the most common interventions were going to the dentist, taking medications, and wearing hearing aids. Our results suggest that full remission of tinnitus is a rare condition, that tinnitus distress on average decreases over time, and that tinnitus characteristics, quality of life, and depression tend to remain unaltered. The high number of interventions and comorbidities displayed minimal association to the changes in tinnitus distress, highlighting the substantial and durable burden of tinnitus sufferers.

PMID:33602995 | DOI:10.1038/s41598-021-83068-5

SOURCE:
Scientific reports

DATE – PUBLISHED:
2021-02-20T09:59:22Z

DATE – DOI: 2021-02-20T09:59:22Z
DATE – PUBMED: 2021 Feb 18
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 19 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/21/21 02:03PM
2021-02-21T14:03:44-05:00

IDENTIFIER:
pmid:33602995,doi:10.1038/s41598-021-83068-5

PUBMED ID:
pubmed:33602995

DOI:
10.1038/s41598-021-83068-5

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33602995/

LINK – DOI:
https://doi.org/10.1038/s41598-021-83068-5

LINK – PUBLISHER:
http://www.nature.com/articles/s41598-021-83068-5

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-21T14:03:44-05:00, www.tinnitustreatmentreport.com.

Pharmacological Evaluation of Drugs in Animal Models of Tinnitus

CATEGORY:
Research

TITLE:
Pharmacological Evaluation of Drugs in Animal Models of Tinnitus

DESCRIPTION:
Despite the pressing need for effective drug treatments for tinnitus, currently, there is no single drug that is approved by the FDA for this purpose. Instead, a wide range of unproven over-the-counter tinnitus remedies are available on the market with little or no benefit for tinnitus but with potential harm and adverse effects. Animal models of tinnitus have played a critical role in exploring the pathophysiology of tinnitus, identifying therapeutic targets and evaluating novel and existing…

CONTENT:
Curr Top Behav Neurosci. 2021 Feb 16. doi: 10.1007/7854_2020_212. Online ahead of print.

ABSTRACT

Despite the pressing need for effective drug treatments for tinnitus, currently, there is no single drug that is approved by the FDA for this purpose. Instead, a wide range of unproven over-the-counter tinnitus remedies are available on the market with little or no benefit for tinnitus but with potential harm and adverse effects. Animal models of tinnitus have played a critical role in exploring the pathophysiology of tinnitus, identifying therapeutic targets and evaluating novel and existing drugs for tinnitus treatment. This review summarises and compares the studies on pharmacological evaluation of tinnitus treatment in different animal models based on the pharmacological properties of the drug and provides insights into future directions for tinnitus drug discovery.

PMID:33590458 | DOI:10.1007/7854_2020_212

SOURCE:
Current topics in behavioral neurosciences

DATE – PUBLISHED:
2021-02-18T21:11:17Z

DATE – DOI: 2021-02-18T21:11:17Z
DATE – PUBMED: 2021 Feb 16
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 16 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/19/21 11:29AM
2021-02-19T11:29:00-05:00

IDENTIFIER:
pmid:33590458,doi:10.1007/7854_2020_212

PUBMED ID:
pubmed:33590458

DOI:
10.1007/7854_2020_212

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33590458/

LINK – DOI:
https://doi.org/10.1007/7854_2020_212

LINK – PUBLISHER:
http://link.springer.com/10.1007/7854_2020_212

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-19T11:29:00-05:00, www.tinnitustreatmentreport.com.

Transient Delivery of a KCNQ2/3-Specific Channel Activator [RL-81] 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

CATEGORY:
Research

TITLE:
Transient Delivery of a KCNQ2/3-Specific Channel Activator 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

DESCRIPTION:
Exposure to loud noise can cause hearing loss and tinnitus in mice and humans. In mice, one major underlying mechanism of noise-induced tinnitus is hyperactivity of auditory brainstem neurons, due at least in part, to decreased Kv7.2/3 (KCNQ2/3) potassium channel activity. In our previous studies, we used a reflex-based mouse model of tinnitus and showed that administration of a non-specific KCNQ channel activator, immediately after noise trauma, prevented the development of noise-induced…

CONTENT:
J Assoc Res Otolaryngol. 2021 Feb 11. doi: 10.1007/s10162-021-00786-3. Online ahead of print.

ABSTRACT

Exposure to loud noise can cause hearing loss and tinnitus in mice and humans. In mice, one major underlying mechanism of noise-induced tinnitus is hyperactivity of auditory brainstem neurons, due at least in part, to decreased Kv7.2/3 (KCNQ2/3) potassium channel activity. In our previous studies, we used a reflex-based mouse model of tinnitus and showed that administration of a non-specific KCNQ channel activator, immediately after noise trauma, prevented the development of noise-induced tinnitus, assessed 1 week after trauma. Subsequently, we developed RL-81, a very potent and highly specific activator of KCNQ2/3 channels. Here, to test the timing window within which RL-81 prevents tinnitus in mice, we modified and employed an operant animal model of tinnitus, where mice are trained to move in response to sound but not move in silence. Mice with behavioral evidence of tinnitus are expected to move in silence. We validated this mouse model by testing the effect of salicylate, which is known to induce tinnitus. We found that transient administration of RL-81 1 week after noise exposure did not affect hearing loss but reduced significantly the percentage of mice with behavioral evidence of tinnitus, assessed 2 weeks after noise exposure. Our results indicate that RL-81 is a promising drug candidate for further development for the treatment of noise-induced tinnitus.

PMID:33575914 | DOI:10.1007/s10162-021-00786-3

SOURCE:
Journal of the Association for Research in Otolaryngology : JARO

DATE – PUBLISHED:
2021-02-11T18:11:11Z

DATE – DOI: 2021-02-11T18:11:11Z
DATE – PUBMED: 2021 Feb 11
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 12 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/12/21 12:44PM
2021-02-12T12:44:10-05:00

IDENTIFIER:
pmid:33575914,doi:10.1007/s10162-021-00786-3

PUBMED ID:
pubmed:33575914

DOI:
10.1007/s10162-021-00786-3

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33575914/

LINK – DOI:
https://doi.org/10.1007/s10162-021-00786-3

LINK – PUBLISHER:
http://link.springer.com/10.1007/s10162-021-00786-3

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-12T12:44:10-05:00, www.tinnitustreatmentreport.com.

Using cortical neuron markers to target cells in the dorsal cochlear nucleus: new means for treatment of bothersome tinnitus?

CATEGORY:
Research

TITLE:
Using cortical neuron markers to target cells in the dorsal cochlear nucleus

DESCRIPTION:
The dorsal cochlear nucleus (DCN) is a region of particular interest for auditory and tinnitus research. Yet, lack of useful genetic markers for in vivo manipulations hinders elucidation of the DCN contribution to tinnitus pathophysiology. This work assesses whether adeno-associated viral vectors (AAV) containing the calcium/calmodulin-dependent protein kinase 2 alpha (CaMKIIα) promoter and a mouse line of nicotinic acetylcholine receptor alpha 2 subunit (Chrna2)-Cre can target specific DCN…

CONTENT:
eNeuro. 2021 Feb 8:ENEURO.0413-20.2020. doi: 10.1523/ENEURO.0413-20.2020. Online ahead of print.

ABSTRACT

The dorsal cochlear nucleus (DCN) is a region of particular interest for auditory and tinnitus research. Yet, lack of useful genetic markers for in vivo manipulations hinders elucidation of the DCN contribution to tinnitus pathophysiology. This work assesses whether adeno-associated viral vectors (AAV) containing the calcium/calmodulin-dependent protein kinase 2 alpha (CaMKIIα ) promoter and a mouse line of nicotinic acetylcholine receptor alpha 2 subunit (Chrna2)-Cre can target specific DCN populations. We found that CaMKIIα cannot be used to target excitatory fusiform DCN neurons as labelled cells showed diverse morphology indicating they belong to different classes of DCN neurons. Light stimulation after driving Channelrhodopsin2 by the CaMKIIα promoter generated spikes in some units but firing rate decreased when light stimulation coincided with sound. Expression and activation of CaMKIIα -eArchaerhodopsin3.0 in the DCN produced inhibition in some units but sound-driven spikes were delayed by concomitant light stimulation. We explored the existence of Cre+ cells in the DCN of Chrna2-Cre mice by hydrogel embedding technique (CLARITY). There were almost no Cre+ cell bodies in the DCN; however, we identified profuse projections arising from the ventral cochlear nucleus (VCN). Anterograde labeling in the VCN revealed projections to the ipsilateral superior olive and contralateral medial nucleus of the trapezoid body (bushy cells); and a second bundle terminating in the DCN, suggesting the latter to be excitatory Chrna2+ T-stellate cells. Exciting Chrna2+ cells increased DCN firing. This work shows that cortical molecular tools may be useful for manipulating the DCN especially for tinnitus studies.Significance statement Cortical neuron markers could be used to label subcortical regions such as the dorsal cochlear nucleus (DCN) that integrates sound and somatosensory input. Here we examine if excitatory (CaMKIIα ) or inhibitory (Chrna2) neuron markers used in neo/paleo-cortex studies label unique DCN populations. We found CaMKIIα to be expressed by different DCN neuron populations (affecting sound sensitive and nonsensitive neurons). The Chrna2 promoter was specifically expressed in excitatory cells of the ventral cochlear nucleus and could drive indirect activity in the DCN. This study highlights novel ways of regulating DCN neuron activity, which can provide new means for treatment of bothersome tinnitus.

PMID:33563600 | DOI:10.1523/ENEURO.0413-20.2020

SOURCE:
eNeuro

DATE – PUBLISHED:
2021-02-09T18:52:33Z

DATE – DOI: 2021-02-09T18:52:33Z
DATE – PUBMED: 2021 Feb 8
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 10 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/10/21 11:52AM
2021-02-10T11:52:09-05:00

IDENTIFIER:
pmid:33563600,doi:10.1523/ENEURO.0413-20.2020

PUBMED ID:
pubmed:33563600

DOI:
10.1523/ENEURO.0413-20.2020

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33563600/

LINK – DOI:
https://doi.org/10.1523/ENEURO.0413-20.2020

LINK – PUBLISHER:
http://eneuro.org/lookup/doi/10.1523/ENEURO.0413-20.2020

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-10T11:52:09-05:00, www.tinnitustreatmentreport.com.

Novel Tinnitus Drug CS0022 Reduces Chronic Tinnitus in Preclinical Study

A pre-clinical tinnitus drug candidate from Cognosetta has shown promising results (and could soon be ready for human trials), according to new research.

Background:

CS0022 (formerly called BMS-191011) is a next generation BK channel opener designed to lower tinnitus volume by regulating the abnormal neural excitability in the central auditory system (CAS)… thereby restoring the proper “balance of excitation and inhibition” necessary for silence.

Cognosetta Inc logo
“Look, they even have a logo!” Image source: Cognosetta Inc

The small company behind CS0022 is Cognosetta, Inc. If you have been following our updates here at Tinnitus Treatment Report, that company name might sound familiar.

Just over a year ago, on January 14, 2020, we posted this: Cognosetta, Inc receives funding from NIH to test a novel therapeutic for treating tinnitus…

CS0022-Class Compounds for the Treatment of Tinnitus

Today, we finally have a follow-up about what is happening with that “novel therapeutic” and its development.

First, a quick primer on the company behind the drug. From the Cognosetta website:

Cognosetta is developing a first-in-market, brain targeted pharmaceutical solution for treating tinnitus […] Our priority is developing a first-in-market medication […] for those with moderate to severe tinnitus […] Our scientists have identified a drug target and drug candidates for improving neurophysiological and behavioral measures of tinnitus and age-related hearing loss. To support the clinical success of these drug candidates our scientists are also advancing quantitative methods for evaluating the efficacy of new drug candidates that can be shared across the preclinical and clinical development stages.

Here is a snapshot of their current pipeline, with CS0022 approaching human trials.

Cognosetta Tinnitus Pipeline
Source: Cognosetta, Inc

How close to human testing and safety trials is CS0022?

Too early to give an exact date.

But, according to a poster presentation from the upcoming 44th Annual ARO MidWinter Virtual Meeting, the drug continues to impress with promising results in preclinical (animal) studies.

Here is a “sneak preview” copy of the upcoming poster presentation – scheduled for Sunday, February 21, 2021:

The BK Channel Opener CS0022 Mitigates Chronic Tinnitus Following Acoustic Trauma

Background: Subjective tinnitus is an audiological and neurological condition that gives rise to a phantom perception of sound. The condition disproportionately impacts individuals with risky occupational or avocational noise exposure. Patients and animal models of tinnitus exhibit altered central auditory system (CAS) neural activity that is presumed to support the tinnitus percept. Broadly, these changes can be characterized by a dysregulation in the balance of excitation and inhibition that leads to neuronal hyperexcitability and synchrony. The large conductance calcium-activated potassium (BK) channel regulates neural excitability in the CAS and other brain regions. Our recent work suggests that systemic administration of a class of BK channel openers reduces salicylate-induced tinnitus in mice through action in the CAS. The main objective of the current study is to determine whether a similar low-exposure treatment also reduces behavioral and neural manifestations of tinnitus in a chronic tinnitus model induced by noise exposure.

Methods: Auditory brainstem response (ABR) thresholds and acoustic startle behavior were assessed in young adult CBA mice before and after acoustic trauma. For acoustic trauma, awake mice were placed in a small, sound transparent cage, and then exposed for 1 hour via free field to a 113 dB SPL, 1 kHz wide band noise centered at 16 kHz. Ten weeks after damaging noise exposure, mice began systemic treatment with a BK channel opener, CS0022. Gap-prepulse inhibition of the acoustic startle reflex (GPIAS) tracked the development of tinnitus and subsequent effects of treatment. A novel machine learning algorithm and computational analysis method was used to determine which mice displayed tinnitus from the GPIAS protocol.

Results: The acoustic trauma procedure caused limited permanent ABR threshold shifts, ranging from none to moderate (~50 dB) in the high frequencies above 16 kHz. Mice were selected for preliminary analysis if they exhibited minimal permanent hearing loss (< 10 dB) and GPIAS evidence of tinnitus at 16 or 32 kHz after acoustic trauma. Six out of the six selected mice showed less suppressed pre-pulse inhibition for the selected tinnitus frequencies following systemic treatment with a BK channel opener. In contrast, treatment did not influence acoustic startle amplitude functions. Pharmacokinetics studies confirmed low exposure in brain. As expected, improved startle selection via machine learning-enhanced computational analysis increased the power and accuracy for identifying tinnitus and treatment effects.

Conclusions: Ongoing neurophysiological and alternate behavioral measures continue to probe treatment outcomes in this model of acoustic trauma-induced chronic tinnitus. Thus far, preliminary outcomes support the idea that treatment with BK channel openers such as the one used in the current study may reduce evidence of tinnitus. There is currently no effective cure for chronic tinnitus, increasing the urgency for studies exploring the utility of promising drug candidates.

Credit to lead author Luisa Scott of Cognosetta Inc and her co-authors at the University of South Florida.

Thanks to their hard work, it looks like we now have another viable first-in-market tinnitus drug candidate to follow…

Plus, a shiny new meme to help spread the word:

Yoda There Is Another Meme

How to get CS0022 updates?

If you want to keep up with promising new tinnitus treatments that are currently in development (including CS0022)… I encourage you to sign up for Tinnitus Treatment Report email updates.

It’s an email newsletter with fresh links and updates (never junk), and… I believe there is no faster way to consistently stay on top of the very latest tinnitus treatment options and scientific breakthroughs.

(It is 100% free, no spam or advertorials, and your information is kept secure and private. Promise.)

Got questions? comments? requests?

Send an email to michael@urgentresearch.com and introduce yourself, say hello.

References and further reading:

  • https://braininitiative.nih.gov/funded-awards/developing-novel-therapeutic-treating-tinnitus
  • https://projectreporter.nih.gov/project_info_details.cfm?aid=9907138&icde=48273554
  • https://www.cognosetta.com
  • https://www.nature.com/articles/srep42433
  • https://aro.societyconference.com/conf/#sessions/conf10001

Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients

CATEGORY:
Research

TITLE:
Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients

DESCRIPTION:
CONCLUSION: Tinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

CONTENT:
Front Neurosci. 2021 Feb 4;14:623520. doi: 10.3389/fnins.2020.623520. eCollection 2020.

ABSTRACT

PURPOSE: Both tinnitus and type 2 diabetes mellitus (T2DM) are linked with cognitive decline and brain dysfunction. This study used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to examine the abnormal cerebral blood flow (CBF) patterns existed in tinnitus patients and potential relationships between the abnormal CBF and cognitive performance. The impact of T2DM on CBF alterations in tinnitus patients was further explored.

METHODS: Sixty tinnitus patients and 40 non-tinnitus subjects were recruited. CBF images were collected and analyzed using ASL perfusion fMRI. Brain regions with CBF alterations between tinnitus patients and non-tinnitus controls were identified by one-way analysis of variance. Interaction effects between tinnitus and T2DM for CBF changes were also selected. Then, correlation analyses were calculated to specify the link between CBF changes and cognitive performance and between CBF changes and diabetic characteristics.

RESULTS: Tinnitus patients showed decreased CBF, primarily in the auditory area and default mode network (DMN), compared with non-tinnitus controls. Decreased CBF in these regions was correlated with executive function and attention. The interaction effect between tinnitus and T2DM was significant in the right medial prefrontal gyrus. Additionally, CBF in the right medial prefrontal gyrus was correlated with tinnitus distress and cognitive performance. In tinnitus patients, Hemoglobin A1c was associated with CBF in the right medial prefrontal gyrus.

CONCLUSION: Tinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

PMID:33633528 | PMC:PMC7902065 | DOI:10.3389/fnins.2020.623520

SOURCE:
Frontiers in neuroscience

DATE – PUBLISHED:
2021-02-04T07:33:52Z

DATE – DOI: 2021-02-04T07:33:52Z
DATE – PUBMED: 2021 Feb 4
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 26 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/26/21 07:59AM
2021-02-26T07:59:11-05:00

IDENTIFIER:
pmid:33633528,pmc:PMC7902065,doi:10.3389/fnins.2020.623520

PUBMED ID:
pubmed:33633528

DOI:
10.3389/fnins.2020.623520

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33633528/

LINK – DOI:
https://doi.org/10.3389/fnins.2020.623520

LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fnins.2020.623520/full

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-26T07:59:11-05:00, www.tinnitustreatmentreport.com.

Altering activity in the peripheral nerve may be a viable target for early pharmaceutical intervention in forms of tinnitus originating in the cochlea

Altering activity in the peripheral nerve may be a viable target for early pharmaceutical intervention in forms of tinnitus originating in the cochlea

Salicylate decreases the spontaneous firing rate of guinea pig auditory nerve fibres

Received 2 October 2020, Revised 26 January 2021, Accepted 29 January 2021, Available online 3 February 2021.

https://www.sciencedirect.com/science/article/pii/S0304394021000835

Spontaneous firing patterns in the medial geniculate nucleus in a guinea pig model of tinnitus

https://www.sciencedirect.com/science/article/abs/pii/S0378595521000241

Spontaneous firing patterns in the medial geniculate nucleus in a guinea pig model of tinnitus

Highlights

– The thalamus may play an important role in tinnitus generation.
– Patterns of neural activity were investigated in animals with and without tinnitus.
– Tinnitus leads to increased spontaneous firing but no change in burst firing.
– This supports theory of dysfunctional sensory gating in tinnitus.

The BDNF Val66 Met polymorphism regulates vulnerability to chronic stress and phantom perception

CATEGORY:
Research

TITLE:
The BDNF Val66 Met polymorphism regulates vulnerability to chronic stress and phantom perception

DESCRIPTION:
Auditory phantom percepts, such as tinnitus, are a heterogeneous condition with great interindividual variations regarding both the percept itself and its concomitants. Tinnitus causes a considerable amount of distress, with as many as 25% of affected people reporting that it interferes with their daily lives. Although previous research gives an idea about the neural correlates of tinnitus-related distress, it cannot explain why some tinnitus patients develop distress and while others are not…

CONTENT:
Prog Brain Res. 2021;260:301-326. doi: 10.1016/bs.pbr.2020.08.005. Epub 2021 Jan 22.

ABSTRACT

Auditory phantom percepts, such as tinnitus, are a heterogeneous condition with great interindividual variations regarding both the percept itself and its concomitants. Tinnitus causes a considerable amount of distress, with as many as 25% of affected people reporting that it interferes with their daily lives. Although previous research gives an idea about the neural correlates of tinnitus-related distress, it cannot explain why some tinnitus patients develop distress and while others are not bothered by their tinnitus. BDNF Val66 Met polymorphism (rs6265) is a known risk factor for affective disorders due to its common frequency and established functionality. To elucidate, we explore the neural activation pattern of tinnitus associated with the BDNF Val66 Met polymorphism using electrophysiological data to assess activity and connectivity changes. A total of 110 participants (55 tinnitus and 55 matched control subjects) were included. In this study, we validate that the BDNF Val66 Met polymorphism plays an important role in the susceptibility to the clinical manifestation of tinnitus-related distress. We demonstrate that Val/Met carriers have increased alpha power in the subgenual anterior cingulate cortex that correlates with distress levels. Furthermore, distress mediates the relationship between BDNF Val66 Met polymorphism and tinnitus loudness. In other words, for Val/Met carriers, the subgenual anterior cingulate cortex sends distress-related information to the parahippocampus, which likely integrates the loudness and distress of the tinnitus percept.

PMID:33637225 | DOI:10.1016/bs.pbr.2020.08.005

SOURCE:
Progress in brain research

DATE – PUBLISHED:
2021-01-22T09:14:30Z

DATE – DOI: 2021-01-22T09:14:30Z
DATE – PUBMED: 2021 Jan 22
DATE OUTPUT MATCHED: True

DATE – ADDED:
Sat, 27 Feb 2021 06:00:00 -0500

DATE – RETRIEVED:
02/27/21 08:23AM
2021-02-27T08:23:52-05:00

IDENTIFIER:
pmid:33637225,doi:10.1016/bs.pbr.2020.08.005

PUBMED ID:
pubmed:33637225

DOI:
10.1016/bs.pbr.2020.08.005

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33637225/

LINK – DOI:
https://doi.org/10.1016/bs.pbr.2020.08.005

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S007961232030131X

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-02-27T08:23:52-05:00, www.tinnitustreatmentreport.com.

Daily Bitemporal Low-frequency Transcranial Random Noise Stimulation in Tinnitus (tRNS2-tin)

CATEGORY:
Clinical Trials

TITLE:
Daily Bitemporal Low-frequency Transcranial Random Noise Stimulation in Tinnitus (tRNS2-tin)

DESCRIPTION:
Condition :   Chronic Tinnitus

Intervention :   Device: lf-tRNS

Sponsor :   University of Regensburg

Recruiting

GUID:
NCT02615600

ID:
NCT02615600

DATE – FIRST POSTED:
Thu, 26 Nov 2015 12:00:00 EST

DATE – LAST UPDATED:
01/20/21 07:32AM

DATE – RETRIEVED:
01/20/21 07:32AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT02615600?type=Intr&cond=Tinnitus&phase=012345&lupd_s=01%2F19%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT02615600

Noise Exposure Alters Glutamatergic and GABAergic Synaptic Connectivity in the Hippocampus and Its Relevance to Tinnitus

CATEGORY:
Research

TITLE:
Noise Exposure Alters Glutamatergic and GABAergic Synaptic Connectivity in the Hippocampus and Its Relevance to Tinnitus

DESCRIPTION:
Accumulating evidence implicates a role for brain structures outside the ascending auditory pathway in tinnitus, the phantom perception of sound. In addition to other factors such as age-dependent hearing loss, high-level sound exposure is a prominent cause of tinnitus. Here, we examined how noise exposure altered the distribution of excitatory and inhibitory synaptic inputs in the guinea pig hippocampus and determined whether these changes were associated with tinnitus. In experiment one,…

CONTENT:
Neural Plast. 2021 Jan 14;2021:8833087. doi: 10.1155/2021/8833087. eCollection 2021.

ABSTRACT

Accumulating evidence implicates a role for brain structures outside the ascending auditory pathway in tinnitus, the phantom perception of sound. In addition to other factors such as age-dependent hearing loss, high-level sound exposure is a prominent cause of tinnitus. Here, we examined how noise exposure altered the distribution of excitatory and inhibitory synaptic inputs in the guinea pig hippocampus and determined whether these changes were associated with tinnitus. In experiment one, guinea pigs were overexposed to unilateral narrow-band noise (98 dB SPL, 2 h). Two weeks later, the density of excitatory (VGLUT-1/2) and inhibitory (VGAT) synaptic terminals in CA1, CA3, and dentate gyrus hippocampal subregions was assessed by immunohistochemistry. Overall, VGLUT-1 density primarily increased, while VGAT density decreased significantly in many regions. Then, to assess whether the noise-induced alterations were persistent and related to tinnitus, experiment two utilized a noise-exposure paradigm shown to induce tinnitus and assessed tinnitus development which was assessed using gap-prepulse inhibition of the acoustic startle (GPIAS). Twelve weeks after sound overexposure, changes in excitatory synaptic terminal density had largely recovered regardless of tinnitus status, but the recovery of GABAergic terminal density was dramatically different in animals expressing tinnitus relative to animals resistant to tinnitus. In resistant animals, inhibitory synapse density recovered to preexposure levels, but in animals expressing tinnitus, inhibitory synapse density remained chronically diminished. Taken together, our results suggest that noise exposure induces striking changes in the balance of excitatory and inhibitory synaptic inputs throughout the hippocampus and reveal a potential role for rebounding inhibition in the hippocampus as a protective factor leading to tinnitus resilience.

PMID:33510780 | PMC:PMC7822664 | DOI:10.1155/2021/8833087

SOURCE:
Neural plasticity

DATE – PUBLISHED:
2021-01-16T00:50:09Z

DATE – DOI: 2021-01-16T00:50:09Z
DATE – PUBMED: 2021 Jan 14
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 29 Jan 2021 06:00:00 -0500

DATE – RETRIEVED:
01/29/21 07:02AM
2021-01-29T07:02:51-05:00

IDENTIFIER:
pmid:33510780,pmc:PMC7822664,doi:10.1155/2021/8833087

PUBMED ID:
pubmed:33510780

DOI:
10.1155/2021/8833087

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33510780/

LINK – DOI:
https://doi.org/10.1155/2021/8833087

LINK – PUBLISHER:
https://www.hindawi.com/journals/np/2021/8833087/

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-01-29T07:02:51-05:00, www.tinnitustreatmentreport.com.

Acoustic and Electrical Stimulation for the Treatment of Tinnitus

CATEGORY:
Clinical Trials

TITLE:
Acoustic and Electrical Stimulation for the Treatment of Tinnitus

DESCRIPTION:
Condition :   Tinnitus

Interventions :   Other: Electrical;   Other: Acoustic

Sponsor :   University of California, Irvine

Recruiting

GUID:
NCT03511807

ID:
NCT03511807

DATE – FIRST POSTED:
Mon, 30 Apr 2018 12:00:00 EDT

DATE – LAST UPDATED:
01/14/21 07:10AM

DATE – RETRIEVED:
01/14/21 07:10AM

LINK – SOURCE:
https://clinicaltrials.gov/ct2/show/NCT03511807?type=Intr&cond=Tinnitus&phase=012345&lupd_s=01%2F13%2F2021&lupd_d=1

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03511807

Towards personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses [Preprint]

https://www.medrxiv.org/content/10.1101/2021.01.11.21249600v1.full-text

Towards personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses
View ORCID ProfileStefan Schoisswohl, View ORCID ProfileBerthold Langguth, View ORCID ProfileTobias Hebel, Mohamed A. Abdelnaim, View ORCID ProfileGregor Volberg, View ORCID ProfileMartin Schecklmann
doi: https://doi.org/10.1101/2021.01.11.21249600
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

BREAKTHROUGH: NAC/HPN-07, also known as the Hough Ear Institute’s NHPN-1010, significantly reduced the incidence of tinnitus, study finds…

Hough Ear Institute tinnitus treatment update:

New research suggests that NAC/HPN-07 treatment (development code name: NHPN-1010) could potentially “reduce, or perhaps reverse, both primary neurodegeneration and excitotoxic trauma in cochleae and prevent or attenuate maladaptive neural plasticity in central auditory pathways.”

In other words, this drug could possibly reduce or even REVERSE tinnitus. At least, that’s what this study is suggesting.

Some more context: this was studied in a blast-induced model of tinnitus. However, the results are no less remarkable… and seem to have broader implications…

Here is a link to the study (which was published moments ago, on January 7, 2021):

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

NAC/HPN-07 is also known by its code name, NHPN-1010 (the much anticipated Hough Ear treatment). The lead author of this paper is Dr. Richard Kopke, CEO of Hough Ear Institute.

More information about this study and the drug (NHPN-1010) will follow soon. Including some answers about when the treatment mentioned in this paper could be offered in human clinical trials. Hmmm…

A strong start to tinnitus science in 2021. Lots happening 🙂

P.S. Keep an eye on this reddit thread for some discussion, opinion, and unfiltered speculation.

P.P.S. For more NAC/HPN-07 updates and breaking tinnitus treatment and science-related developments… please remember to sign up for email updates (it’s free and first issue will be sent out soon). Even better, share TinnitusTreatmentReport.com with others who might find this information helpful, too…

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243903

Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus
Jianzhong Lu,Matthew B. West,Xiaoping Du,Qunfeng Cai,Donald L. Ewert,Weihua Cheng,Don Nakmali,Wei Li,Xiangping Huang,Richard D. Kopke
Published: January 7, 2021https://doi.org/10.1371/journal.pone.0243903

Low-Level Laser Therapy as a Therapeutic Strategy for Patients With Tinnitus: Not Yet Proven

CATEGORY:
Research

TITLE:
Effects of Low-Level Laser Therapy as a Therapeutic Strategy for Patients With Tinnitus: A Systematic Review

DESCRIPTION:
Purpose This systematic review aimed to analyze the effects of low-level laser therapy (LLLT) on the severity of tinnitus when compared to no therapy or other modalities of therapies. Method A systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under the Registration Number CRD42019119376. A search was performed in each of the following databases: EMBASE, LILACS, PubMed, Science Direct, Scopus, Web of Science, Google Scholar, and…

CONTENT:
J Speech Lang Hear Res. 2020 Dec 29:1-20. doi: 10.1044/2020_JSLHR-20-00066. Online ahead of print.

ABSTRACT

Purpose This systematic review aimed to analyze the effects of low-level laser therapy (LLLT) on the severity of tinnitus when compared to no therapy or other modalities of therapies. Method A systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under the Registration Number CRD42019119376. A search was performed in each of the following databases: EMBASE, LILACS, PubMed, Science Direct, Scopus, Web of Science, Google Scholar, and ProQuest. The inclusion criteria consisted of studies in adults over 16 years of age, randomized clinical trials in which subjects presented chronic (≥ 6 months) and subjective tinnitus (unilateral or bilateral) as well as with or without bilateral sensorineural hearing loss, and studies that used only LLLT for treatment of tinnitus compared to no-therapy group or other modalities of therapy. No language or time restrictions were stipulated. The references were managed by Endnote Web and Rayyan QCRI. Results After the screening process, seven studies remained that attained the eligibility criteria. Regarding the risk of bias, only one study was categorized as low risk of bias; the six remaining studies were classified as moderate risk of bias. The seven included studies mainly assessed the LLLT effects on tinnitus by Visual Analogue Scale, Tinnitus Handicap Inventory, pitch and loudness matching, minimum masking level, and pure-tone audiometry. All the seven selected studies found different degrees of significant results regarding tinnitus severity; however, there was no consensus among the results. Conclusion Even though the LLLT showed positive effects in the tinnitus severity in some studies, it is not possible yet to make any recommendation over its uses for the treatment of tinnitus severity.

PMID:33375822 | DOI:10.1044/2020_JSLHR-20-00066

SOURCE:
Journal of speech, language, and hearing research : JSLHR

DATE – PUBLISHED:
2020-12-30T02:46:47Z

DATE – DOI: 2020-12-30T02:46:47Z
DATE – PUBMED: 2020 Dec 29
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 30 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/30/20 11:58AM
2020-12-30T11:58:50-05:00

IDENTIFIER:
pmid:33375822,doi:10.1044/2020_JSLHR-20-00066

PUBMED ID:
pubmed:33375822

DOI:
10.1044/2020_JSLHR-20-00066

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33375822/

LINK – DOI:
https://doi.org/10.1044/2020_JSLHR-20-00066

LINK – PUBLISHER:
http://pubs.asha.org/doi/10.1044/2020_JSLHR-20-00066

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-30T11:58:50-05:00, www.tinnitustreatmentreport.com.

ATP-sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem

CATEGORY:
Research

TITLE:
ATP-sensitive K+ channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem

DESCRIPTION:
KEY POINTS: Cartwheel neurons provide potent inhibition to fusiform neurons in the dorsal cochlear nucleus (DCN). Most cartwheel neurons fire action potentials spontaneously, but the ion channels responsible for this intrinsic activity are unknown. We investigated the ion channels responsible for the intrinsic firing of cartwheel neurons and the stable resting membrane potential found in a fraction of these neurons (quiet neurons) Among the ion channels controlling membrane potential of…

CONTENT:
J Physiol. 2020 Dec 28. doi: 10.1113/JP280233. Online ahead of print.

ABSTRACT

KEY POINTS: Cartwheel neurons provide potent inhibition to fusiform neurons in the dorsal cochlear nucleus (DCN). Most cartwheel neurons fire action potentials spontaneously, but the ion channels responsible for this intrinsic activity are unknown. We investigated the ion channels responsible for the intrinsic firing of cartwheel neurons and the stable resting membrane potential found in a fraction of these neurons (quiet neurons) Among the ion channels controlling membrane potential of cartwheel neurons, the presence of open ATP-sensitive potassium channels (KATP ) is responsible for the existence of quiet neurons. Our results pinpoint KATP channel modulation as a critical factor controlling the firing of cartwheel neurons. Hence, it is a crucial channel influencing the balance of excitation and inhibition in the DCN.

ABSTRACT: Cartwheel neurons from the dorsal cochlear nucleus (DCN) are glycinergic interneurons and the primary source of inhibition on the fusiform neurons, DCN’s principal excitatory neuron. Most cartwheel neurons present spontaneous firing (active neurons), producing a steady inhibitory tone on fusiform neurons. In contrast, a small fraction of these neurons do not fire spontaneously (quiet neurons). Hyperactivity of fusiform neurons is seen in animals with behavioral evidence of tinnitus. Because of its relevance in controlling the excitability of fusiform neurons, we investigated the ion channels responsible for the spontaneous firing of cartwheel neurons in DCN slices from rats. We found that quiet neurons presented an outward conductance not seen in active neurons, which generates a stable resting potential. This current was sensitive to tolbutamide, an ATP-sensitive potassium channel (KATP ) antagonist. After inhibition with tolbutamide, quiet neurons start to fire spontaneously, while the active neurons were not affected. On the other hand, in active neurons, KATP agonist diazoxide activated a conductance similar to quiet neurons’ KATP conductance and stopped spontaneous firing. According to the effect of KATP channels on CW neuron firing, glycinergic neurotransmission in DCN was increased by tolbutamide and decreased by diazoxide. Our results reveal a role of KATP channels in controlling the spontaneous firing of neurons not involved in fuel homeostasis. This article is protected by copyright. All rights reserved.

PMID:33369743 | DOI:10.1113/JP280233

SOURCE:
The Journal of physiology

DATE – PUBLISHED:
2020-12-28T20:55:32Z

DATE – DOI: 2020-12-28T20:55:32Z
DATE – PUBMED: 2020 Dec 28
DATE OUTPUT MATCHED: True

DATE – ADDED:
Mon, 28 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/29/20 12:19AM
2020-12-29T00:19:56-05:00

IDENTIFIER:
pmid:33369743,doi:10.1113/JP280233

PUBMED ID:
pubmed:33369743

DOI:
10.1113/JP280233

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33369743/

LINK – DOI:
https://doi.org/10.1113/JP280233

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1113/JP280233

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-29T00:19:56-05:00, www.tinnitustreatmentreport.com.

Systematic review and meta-analysis of late auditory evoked potentials as a candidate biomarker in the assessment of tinnitus

CATEGORY:
Research

TITLE:
Systematic review and meta-analysis of late auditory evoked potentials as a candidate biomarker in the assessment of tinnitus

DESCRIPTION:
Subjective tinnitus, the perception of sound in the absence of any sound source, is routinely assessed using questionnaires. The subjective nature of these tools hampers objective evaluation of tinnitus presence, severity and treatment effects. Late auditory evoked potentials (LAEPs) might be considered as a potential biomarker for assessing tinnitus complaints. Using a multivariate meta-analytic model including data from twenty-one studies, we determined the LAEP components differing…

CONTENT:
PLoS One. 2020 Dec 17;15(12):e0243785. doi: 10.1371/journal.pone.0243785. eCollection 2020.

ABSTRACT

Subjective tinnitus, the perception of sound in the absence of any sound source, is routinely assessed using questionnaires. The subjective nature of these tools hampers objective evaluation of tinnitus presence, severity and treatment effects. Late auditory evoked potentials (LAEPs) might be considered as a potential biomarker for assessing tinnitus complaints. Using a multivariate meta-analytic model including data from twenty-one studies, we determined the LAEP components differing systematically between tinnitus patients and controls. Results from this model indicate that amplitude of the P300 component is lower in tinnitus patients (standardized mean difference (SMD) = -0.83, p < 0.01), while latency of this component is abnormally prolonged in this population (SMD = 0.97, p < 0.01). No other investigated LAEP components were found to differ between tinnitus and non-tinnitus subjects. Additional sensitivity analyses regarding differences in experimental conditions confirmed the robustness of these results. Differences in age and hearing levels between the two experimental groups might have a considerable impact on LAEP outcomes and should be carefully considered in future studies. Although we established consistent differences in the P300 component between tinnitus patients and controls, we could not identify any evidence that this component might covary with tinnitus severity. We conclude that out of several commonly assessed LAEP components, only the P300 can be considered as a potential biomarker for subjective tinnitus, although more research is needed to determine its relationship with subjective tinnitus measures. Future trials investigating experimental tinnitus therapies should consider including P300 measurements in the evaluation of treatment effect. PMID:33332414 | DOI:10.1371/journal.pone.0243785 SOURCE: PloS one DATE - PUBLISHED: 2020-12-17T19:56:22Z DATE - DOI: 2020-12-17T19:56:22Z DATE - PUBMED: 2020 Dec 17 DATE OUTPUT MATCHED: True DATE - ADDED: Thu, 17 Dec 2020 06:00:00 -0500 DATE - RETRIEVED: 12/17/20 06:44PM 2020-12-17T18:44:08-05:00 IDENTIFIER: pmid:33332414,doi:10.1371/journal.pone.0243785 PUBMED ID: pubmed:33332414 DOI: 10.1371/journal.pone.0243785 LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33332414/ LINK - DOI: https://doi.org/10.1371/journal.pone.0243785 LINK - PUBLISHER: https://dx.plos.org/10.1371/journal.pone.0243785 REFERENCES: Tinnitus Treatment Report, Urgent Research, 2020-12-17T18:44:08-05:00, www.tinnitustreatmentreport.com.

Gray matter declines with age and hearing loss, but is partially maintained in tinnitus

CATEGORY:
Research

TITLE:
Gray matter declines with age and hearing loss, but is partially maintained in tinnitus

DESCRIPTION:
The impact of age-related hearing loss extends beyond the auditory pathway and impacts brain areas related to cognitive impairment and even dementia. The presence of tinnitus, a sensation of sound that frequently co-occurs with hearing loss, is additionally linked to cognitive decline. Interestingly, structural neuroimaging studies have reported that hearing loss may precede or modulate the onset of cognitive impairment. In this study, we aimed to disentangle the effects of age, hearing loss,…

CONTENT:
Sci Rep. 2020 Dec 11;10(1):21801. doi: 10.1038/s41598-020-78571-0.

ABSTRACT

The impact of age-related hearing loss extends beyond the auditory pathway and impacts brain areas related to cognitive impairment and even dementia. The presence of tinnitus, a sensation of sound that frequently co-occurs with hearing loss, is additionally linked to cognitive decline. Interestingly, structural neuroimaging studies have reported that hearing loss may precede or modulate the onset of cognitive impairment. In this study, we aimed to disentangle the effects of age, hearing loss, and tinnitus on gray matter structure. In total, 39 participants with hearing loss and tinnitus, 21 with hearing loss but without tinnitus, and 39 controls were included in this voxel- and surface-based morphometry MRI study. Whole brain volume and surface thickness measures were compared between the groups. Age-related gray matter volume decline was observed in all groups. Several brain areas showed smaller gray matter volume and cortical surface thickness in hearing loss without tinnitus, relative to controls. This reduction was observed both within and outside of the auditory pathway. Interestingly, these reductions were not observed in participants with tinnitus, who had similar hearing loss and were of similar age. Since we have tools to improve hearing loss, hearing screening may aid in the battle against cognitive decline.

PMID:33311548 | DOI:10.1038/s41598-020-78571-0

SOURCE:
Scientific reports

DATE – PUBLISHED:
2020-12-11T12:06:06Z

DATE – DOI: 2020-12-11T12:06:06Z
DATE – PUBMED: 2020 Dec 11
DATE OUTPUT MATCHED: True

DATE – ADDED:
Mon, 14 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/15/20 01:37AM
2020-12-15T01:37:27-05:00

IDENTIFIER:
pmid:33311548,doi:10.1038/s41598-020-78571-0

PUBMED ID:
pubmed:33311548

DOI:
10.1038/s41598-020-78571-0

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33311548/

LINK – DOI:
https://doi.org/10.1038/s41598-020-78571-0

LINK – PUBLISHER:
http://www.nature.com/articles/s41598-020-78571-0

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-15T01:37:27-05:00, www.tinnitustreatmentreport.com.

Purinergic signaling controls spontaneous activity in the auditory system throughout early development

https://www.jneurosci.org/content/early/2020/12/09/JNEUROSCI.2178-20.2020

Purinergic signaling controls spontaneous activity in the auditory system throughout early development
Travis A. Babola, Sally Li, Zhirong Wang, Calvin J. Kersbergen, Ana Belén Elgoyhen, Thomas M. Coate and Dwight E. Bergles
Journal of Neuroscience 10 December 2020, JN-RM-2178-20; DOI: https://doi.org/10.1523/JNEUROSCI.2178-20.2020

Otonomy expects to start Phase 2 trial of OTO-313 in tinnitus in first quarter of 2021

https://investors.otonomy.com/news-releases/news-release-details/otonomy-provides-update-otividexr-and-oto-313-programs

https://www.globenewswire.com/news-release/2020/11/30/2136417/0/en/Otonomy-Provides-Update-on-OTIVIDEX-and-OTO-313-Programs.html

Otonomy expects to start Phase 2 trial of OTO-313 in tinnitus in first quarter of 2021

Tinnitus and auditory cortex: using adapted functional near-infrared spectroscopy to measure resting-state functional connectivity

CATEGORY:
Research

TITLE:
Tinnitus and auditory cortex: using adapted functional near-infrared spectroscopy to measure resting-state functional connectivity

DESCRIPTION:
CONCLUSION: While many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.

CONTENT:
Neuroreport. 2020 Nov 27. doi: 10.1097/WNR.0000000000001561. Online ahead of print.

ABSTRACT

OBJECTIVE: Tinnitus, phantom sound perception, arises from aberrant brain activity within auditory cortex. In tinnitus animal models, auditory cortex neurons show increased spontaneous firing and neural synchrony. In humans, similar hyperactivation in auditory cortex has been displayed with functional near-infrared spectroscopy (fNIRS). Resting-state functional connectivity (RSFC) or increased connectivity between brain regions has also been shown in tinnitus using fNIRS. However, current fNIRS technology utilizes infrared (IR)-sources and IR-detectors placed on the scalp that restricts (~3 cm depth IR penetration) signal capture to outer cerebral cortex due to skin and skull bone. To overcome this limitation, in this proof of concept study, we adapted fNIRS probes to fit in the external auditory canal (EAC) to physically place IR-probes deeper within the skull thereby extracting neural signals from deeper auditory cortex.

METHODS: Twenty adults with tinnitus and 20 nontinnitus controls listened to periods of silence and broadband noise before and after 5 min of silence to calculate RSFC. Concurrent scalp probes over auditory cortex and an adapted probe placed in the right EAC were utilized.

RESULTS: For standard probes, left and right auditory cortex in tinnitus showed increased RSFC to each other and to other nonauditory cortices. Interestingly, adapted fNIRS probes showed trends toward increased RSFC.

CONCLUSION: While many areas for the adapted probes did not reach significance, these data using a highly innovative and newly created probe adapting fNIRS technology to the EAC substantiates our previously published data in human tinnitus and concurrently validates this technology as a useful and expanded brain imaging modality.

PMID:33252478 | DOI:10.1097/WNR.0000000000001561

SOURCE:
Neuroreport

DATE – PUBLISHED:
2020-11-30T19:37:58Z

DATE – DOI: 2020-11-30T19:37:58Z
DATE – PUBMED: 2020 Nov 27
DATE OUTPUT MATCHED: True

DATE – ADDED:
Mon, 30 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/30/20 03:14PM
2020-11-30T15:14:28-05:00

IDENTIFIER:
pmid:33252478,doi:10.1097/WNR.0000000000001561

PUBMED ID:
pubmed:33252478

DOI:
10.1097/WNR.0000000000001561

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33252478/

LINK – DOI:
https://doi.org/10.1097/WNR.0000000000001561

LINK – PUBLISHER:
https://journals.lww.com/10.1097/WNR.0000000000001561

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-30T15:14:28-05:00, www.tinnitustreatmentreport.com.

Switching Tinnitus-On: Maps and source localization of spontaneous EEG

CATEGORY:
Research

TITLE:
Switching Tinnitus-On: Maps and source localization of spontaneous EEG

DESCRIPTION:
CONCLUSIONS: The emergence of new delta, theta and gamma band sources in the inferior temporal gyrus (BA 20), middle temporal gyrus (BA 21) and lateral perirhinal cortex (BA 36) plus the appearance of new delta and theta sources in the ventral entorhinal cortex (BA28) and anterior pole of the temporal lobe (BA 38) may comprise a network capable of evoking the phantom sound of tinnitus by simultaneously engaging brain regions involved in memory, sound recognition, and distress which together…

CONTENT:
Clin Neurophysiol. 2020 Nov 23;132(2):345-357. doi: 10.1016/j.clinph.2020.10.023. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify the spectrotemporal changes and sources in patients that could “turn on” tinnitus with multichannel electroencephalography (EEG) system.

METHODS: Multichannel EEG was recorded from six patients during the Tinnitus-On and Tinnitus-Off states. The EEG power spectrum and eLORETA-based sources were measured.

RESULTS: There was a global increase in delta and theta during Tinnitus-On plus large changes in alpha 1 and alpha 2. During the Tinnitus-On state, many new sources in delta, theta, alpha 1 and gamma bands emerged in the opposite hemisphere in the inferior temporal gyrus (Brodmann area, BA 20), middle temporal gyrus (BA 21), lateral perirhinal cortex (BA 36), ventral entorhinal cortex (BA 28) and anterior pole of the temporal gyrus (BA 38).

CONCLUSIONS: The emergence of new delta, theta and gamma band sources in the inferior temporal gyrus (BA 20), middle temporal gyrus (BA 21) and lateral perirhinal cortex (BA 36) plus the appearance of new delta and theta sources in the ventral entorhinal cortex (BA28) and anterior pole of the temporal lobe (BA 38) may comprise a network capable of evoking the phantom sound of tinnitus by simultaneously engaging brain regions involved in memory, sound recognition, and distress which together contribute to tinnitus severity.

SIGNIFICANCE: The sudden appearance of new sources of activity in the opposite hemisphere within the inferior temporal gyrus, middle temporal gyrus and perirhinal cortex may initiate the perception of tinnitus perception.

PMID:33450557 | DOI:10.1016/j.clinph.2020.10.023

SOURCE:
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

DATE – PUBLISHED:
2020-11-23T17:15:55Z

DATE – DOI: 2020-11-23T17:15:55Z
DATE – PUBMED: 2020 Nov 23
DATE OUTPUT MATCHED: True

DATE – ADDED:
Fri, 15 Jan 2021 06:00:00 -0500

DATE – RETRIEVED:
01/16/21 01:04AM
2021-01-16T01:04:05-05:00

IDENTIFIER:
pmid:33450557,doi:10.1016/j.clinph.2020.10.023

PUBMED ID:
pubmed:33450557

DOI:
10.1016/j.clinph.2020.10.023

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33450557/

LINK – DOI:
https://doi.org/10.1016/j.clinph.2020.10.023

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1388245720305575

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2021-01-16T01:04:05-05:00, www.tinnitustreatmentreport.com.

Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective

CATEGORY:
Research

TITLE:
Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective

DESCRIPTION:
Cannabis has been used for centuries for recreational and therapeutic purposes. Whereas, the recreative uses are based on the psychotropic effect of some of its compounds, its therapeutic effects range over a wide spectrum of actions, most of which target the brain or the immune system. Several studies have found cannabinoid receptors in the auditory system, both at peripheral and central levels, thus raising the interest in cannabinoid signaling in hearing, and especially in tinnitus, which is…

CONTENT:
Front Neurol. 2020 Nov 23;11:505995. doi: 10.3389/fneur.2020.505995. eCollection 2020.

ABSTRACT

Cannabis has been used for centuries for recreational and therapeutic purposes. Whereas, the recreative uses are based on the psychotropic effect of some of its compounds, its therapeutic effects range over a wide spectrum of actions, most of which target the brain or the immune system. Several studies have found cannabinoid receptors in the auditory system, both at peripheral and central levels, thus raising the interest in cannabinoid signaling in hearing, and especially in tinnitus, which is affected also by anxiety, memory, and attention circuits where cannabinoid effects are well described. Available studies on animal models of tinnitus suggest that cannabinoids are not likely to be helpful in tinnitus treatment and could even be harmful. However, the pharmacology of cannabinoids is very complex, and most studies focused on neural CB1R-based responses. Cannabinoid effects on the immune system (where CB2Rs predominate) are increasingly recognized as essential in understanding nervous system pathological responses, and data on immune cannabinoid targets have emerged in the auditory system as well. In addition, nonclassical cannabinoid targets (such as TRP channels) appear to play an important role in the auditory system as well. This review will focus on neuroimmunological mechanisms for cannabinoid effects and their possible use as protective and therapeutic agents in the ear and auditory system, especially in tinnitus.

PMID:33329293 | PMC:PMC7719758 | DOI:10.3389/fneur.2020.505995

SOURCE:
Frontiers in neurology

DATE – PUBLISHED:
2020-11-23T06:22:31Z

DATE – DOI: 2020-11-23T06:22:31Z
DATE – PUBMED: 2020 Nov 23
DATE OUTPUT MATCHED: True

DATE – ADDED:
Thu, 17 Dec 2020 06:00:00 -0500

DATE – RETRIEVED:
12/17/20 01:41PM
2020-12-17T13:41:18-05:00

IDENTIFIER:
pmid:33329293,pmc:PMC7719758,doi:10.3389/fneur.2020.505995

PUBMED ID:
pubmed:33329293

DOI:
10.3389/fneur.2020.505995

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33329293/

LINK – DOI:
https://doi.org/10.3389/fneur.2020.505995

LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fneur.2020.505995/full

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-12-17T13:41:18-05:00, www.tinnitustreatmentreport.com.

Objective measurement of tinnitus using functional near-infrared spectroscopy and machine learning

CATEGORY:
Research

TITLE:
Objective measurement of tinnitus using functional near-infrared spectroscopy and machine learning

DESCRIPTION:
Chronic tinnitus is a debilitating condition which affects 10-20% of adults and can severely impact their quality of life. Currently there is no objective measure of tinnitus that can be used clinically. Clinical assessment of the condition uses subjective feedback from individuals which is not always reliable. We investigated the sensitivity of functional near-infrared spectroscopy (fNIRS) to differentiate individuals with and without tinnitus and to identify fNIRS features associated with…

CONTENT:
PLoS One. 2020 Nov 18;15(11):e0241695. doi: 10.1371/journal.pone.0241695. eCollection 2020.

ABSTRACT

Chronic tinnitus is a debilitating condition which affects 10-20% of adults and can severely impact their quality of life. Currently there is no objective measure of tinnitus that can be used clinically. Clinical assessment of the condition uses subjective feedback from individuals which is not always reliable. We investigated the sensitivity of functional near-infrared spectroscopy (fNIRS) to differentiate individuals with and without tinnitus and to identify fNIRS features associated with subjective ratings of tinnitus severity. We recorded fNIRS signals in the resting state and in response to auditory or visual stimuli from 25 individuals with chronic tinnitus and 21 controls matched for age and hearing loss. Severity of tinnitus was rated using the Tinnitus Handicap Inventory and subjective ratings of tinnitus loudness and annoyance were measured on a visual analogue scale. Following statistical group comparisons, machine learning methods including feature extraction and classification were applied to the fNIRS features to classify patients with tinnitus and controls and differentiate tinnitus at different severity levels. Resting state measures of connectivity between temporal regions and frontal and occipital regions were significantly higher in patients with tinnitus compared to controls. In the tinnitus group, temporal-occipital connectivity showed a significant increase with subject ratings of loudness. Also in this group, both visual and auditory evoked responses were significantly reduced in the visual and auditory regions of interest respectively. Naïve Bayes classifiers were able to classify patients with tinnitus from controls with an accuracy of 78.3%. An accuracy of 87.32% was achieved using Neural Networks to differentiate patients with slight/ mild versus moderate/ severe tinnitus. Our findings show the feasibility of using fNIRS and machine learning to develop an objective measure of tinnitus. Such a measure would greatly benefit clinicians and patients by providing a tool to objectively assess new treatments and patients’ treatment progress.

PMID:33206675 | DOI:10.1371/journal.pone.0241695

SOURCE:
PloS one

DATE – PUBLISHED:
2020-11-18T18:26:43Z

DATE – DOI: 2020-11-18T18:26:43Z
DATE – PUBMED: 2020 Nov 18
DATE OUTPUT MATCHED: True

DATE – ADDED:
Wed, 18 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/18/20 06:49PM
2020-11-18T18:49:54-05:00

IDENTIFIER:
pmid:33206675,doi:10.1371/journal.pone.0241695

PUBMED ID:
pubmed:33206675

DOI:
10.1371/journal.pone.0241695

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33206675/

LINK – DOI:
https://doi.org/10.1371/journal.pone.0241695

LINK – PUBLISHER:
https://dx.plos.org/10.1371/journal.pone.0241695

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-18T18:49:54-05:00, www.tinnitustreatmentreport.com.

Tinnitus impairs segregation of competing speech in normal-hearing listeners

CATEGORY:
Research

TITLE:
Tinnitus impairs segregation of competing speech in normal-hearing listeners

DESCRIPTION:
Many tinnitus patients report difficulties understanding speech in noise or competing talkers, despite having “normal” hearing in terms of audiometric thresholds. The interference caused by tinnitus is more likely central in origin. Release from informational masking (more central in origin) produced by competing speech may further illuminate central interference due to tinnitus. In the present study, masked speech understanding was measured in normal hearing listeners with or without tinnitus….

CONTENT:
Sci Rep. 2020 Nov 16;10(1):19851. doi: 10.1038/s41598-020-76942-1.

ABSTRACT

Many tinnitus patients report difficulties understanding speech in noise or competing talkers, despite having “normal” hearing in terms of audiometric thresholds. The interference caused by tinnitus is more likely central in origin. Release from informational masking (more central in origin) produced by competing speech may further illuminate central interference due to tinnitus. In the present study, masked speech understanding was measured in normal hearing listeners with or without tinnitus. Speech recognition thresholds were measured for target speech in the presence of multi-talker babble or competing speech. For competing speech, speech recognition thresholds were measured for different cue conditions (i.e., with and without target-masker sex differences and/or with and without spatial cues). The present data suggest that tinnitus negatively affected masked speech recognition even in individuals with no measurable hearing loss. Tinnitus severity appeared to especially limit listeners’ ability to segregate competing speech using talker sex differences. The data suggest that increased informational masking via lexical interference may tax tinnitus patients’ central auditory processing resources.

PMID:33199782 | DOI:10.1038/s41598-020-76942-1

SOURCE:
Scientific reports

DATE – PUBLISHED:
2020-11-16T11:14:10Z

DATE – DOI: 2020-11-16T11:14:10Z
DATE – PUBMED: 2020 Nov 16
DATE OUTPUT MATCHED: True

DATE – ADDED:
Tue, 17 Nov 2020 06:00:00 -0500

DATE – RETRIEVED:
11/17/20 12:27PM
2020-11-17T12:27:23-05:00

IDENTIFIER:
pmid:33199782,doi:10.1038/s41598-020-76942-1

PUBMED ID:
pubmed:33199782

DOI:
10.1038/s41598-020-76942-1

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33199782/

LINK – DOI:
https://doi.org/10.1038/s41598-020-76942-1

LINK – PUBLISHER:
http://www.nature.com/articles/s41598-020-76942-1

REFERENCES:
Tinnitus Treatment Report, Urgent Research, 2020-11-17T12:27:23-05:00, www.tinnitustreatmentreport.com.

Back to top