TAMPA, Fla. (Feb. 11, 2015) - A successful treatment for age-related hearing loss (ARHL) is a step closer to reality, thanks to a group of researchers from the University of South Florida. The research team comprised of faculty and students has been awarded $400,000 by Autifony Therapeutics, Ltd, a company based in the United Kingdom, to test a new drug the company developed for ARHL. The Institutional Review Board (IRB) has approved the year-long, Phase II clinical trial, and patients are being screened for the study that is expected to start in the early spring.
ARHL, also called "presbycusis," is the number one communication disorder and most common neurodegenerative condition affecting older Americans. While ARHL directly and negatively affects quality of life for older people, severe ARHL has recently been linked to the earlier onset of dementia. ARHL is estimated to affect 10 percent of the population and there are no currently approved treatments.
"The most common complaint among people with ARHL is difficulty hearing speech where there is a lot of background noise, such as in a restaurant," says Dr. Robert Frisina, Jr., the study's principal investigator and director of the USF Global Center for Hearing & Speech Research. "Currently, there are no U.S. Food and Drug Administration-approved treatments for permanent hearing loss, including ARHL, despite its prevalence. Over 40 million people in the U.S. alone have ARHL or other forms of permanent hearing loss."
The test drug, called "AUT0063," has been tested in aging animals with hearing loss and in a small, Phase I clinical trial with humans. With USF designated by the company as the "lead clinical trial site," the USF researchers will play a critical role in the Phase II research.
A Phase II clinical trial is conducted with larger groups of patients after researchers have tested a new drug or treatment for the first time in a Phase I clinical trial to evaluate its safety, determine a safe dosage range, and identify any side effects. A Phase II trial focuses on documenting the drug's effectiveness over time and also adds additional safety data.
AUT0063 is aimed at modifying portions of the brain that decline with age and cause age-related hearing loss, explains Frisina, who is also a professor in USF's College of Engineering and College of Behavioral & Community Sciences.
"There are many fast-firing neurons in the auditory systems, but they decline in efficiency with age," he explains. "Within the auditory system are channels called voltage-gated potassium channels. These channels are specific for potassium and sensitive to voltage changes and play a crucial role in nerve cell activity."
The channels are involved in how the brain codes timing features of sound perception, says Dr. Victoria Williams-Sanchez, study co-investigator and Chief Coordinator of USF's Auditory Rehabilitation & Clinical Trials Laboratory in the College of Behavioral & Community Sciences.
"The ability to discriminate timing features of sound is very important for speech and music perception," says Williams-Sanchez. "But the timing ability declines with age, and from the previous, pre-clinical studies with animal models that we know that the potassium channels are one of the biological mechanisms underlying ARHL."
According to Frisina, the voltage-gated potassium channel Kv3.1 is an important channel for hearing, but its expression declines with age. AUT0063 modulates and increases the activity levels of the Kv3.1 voltage-gated channels found in the central auditory system, the parts of the brain used for hearing. Patients volunteering for the study will take AUT0063 orally each morning and be evaluated periodically during the year of study.
"Our primary goal is to investigate the potential therapeutic roles of modulating the action of voltage-gated potassium channels in the brain in order to mitigate some of the key elements of ARHL to improve speech-in-noise recognition and processing," says Frisina.
For example, people with ARHL have difficulty understanding components of speech, often having difficulty telling the difference between consonants, such as a "b" and a "p." Telling the difference between these two sounds depends partly on the speed of processing capacity.
When AUT0063 was tested in "preclinical" trials on animals with hearing loss, the studies demonstrated that AUT0063 "significantly improved auditory temporal processing" in the test animals and "has the potential for treating age-related hearing impairment in humans."
The USF Phase II clinical trial team testing AUT0063 also includes Dr. Terry Chisolm, Vice Provost and Professor of Communication Sciences and Disorders, and Dr. Paul Boyev, Medical Director & Co-Investigator, Professor of Otolaryngology and Head & Neck Surgery, USF College of Medicine. The team also includes graduate students Amanda Brandino and Celia D. Riffle, and undergraduate Laura Westermann.
The University of South Florida is a high-impact, global research university dedicated to student success. USF is a Top 50 research university among both public and private institutions nationwide in total research expenditures, according to the National Science Foundation. Serving nearly 48,000 students, the USF System has an annual budget of $1.5 billion and an annual economic impact of $4.4 billion. USF is a member of the American Athletic Conference.