“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.”
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