Novel Therapeutic for Cochlear Hair Cell Regeneration and Hearing Restoration
Abstract
Objectives and Rationale: Hough Ear Institute (HEI) and our commercial partner, Otologic Pharmaceutics, Inc. (OPI) have joined together with the objective of developing a drug that can restore hearing loss, specifically noise-induced hearing loss (NIHL). Unfortunately, because hearing loss is related to a loss of sensory hair cells (HC) in the inner ear, which are unable to regenerate, deafness is irreversible in humans. Using silencing RNA (siRNA) technology, HEI and OPI have developed a drug to regenerate lost HC by targeting a pathway involved in HC regeneration. The medicine could be administered in the ear in an outpatient setting. The objectives of HEI and OPI’s proposed project address the Hearing and Balance Research Award’s Focus Area of “demonstrating the regeneration of functional hair cells which has the potential to lead to a U.S. Food and Drug Administration (FDA)-approved therapeutic.” This project will allow the HEI and OPI research and development team to determine the best dose, composition, and method of delivery of our drug, Hes1 siRNA (siHes1) in a safe composition that reproducibly regenerates lost HC in the cochlea and significantly restores hearing in noise-deafened animals. The aims of our project include: (1) Determine the dose of siHes1 that produces the most significant improvement in hearing in an acute NIHL model. (2) Determine a concentration of HEI-115, a synergistic compound that greatly enhances the effectiveness of our siHes1 compound. (3) Determine the best delivery approach that will provide the most hearing restoration in an acute NIHL model. (4) Determine the effects of our product in a chronic deafening model. Applicability, Potential Impact, and Patient Type: HEI’s prime focus is the treatment of NIHL, a major cause of disability in military personnel. Hearing loss is a significant problem in the military, impacting the Warfighter, our Veterans, and their families. NIHL is the second most common Service-connected disability next to tinnitus, another ear-related disability, and negatively impacts combat performance. Over 50% of Afghanistan or Iraq war combat Soldiers have hearing loss attributable to combat noise exposure. Beyond the military, 360 million people worldwide have disabling hearing loss, resulting in an annual cost of hearing loss averaging $750 billion every year. This includes 10 million US civilians with NIHL among 22 million workers exposed to loud noise annually. Currently, there are no available treatments that can restore lost HC. By developing a drug that can restore HC, hearing loss can be reversed and the potential to positively impact the lives of military personnel and civilians alike is dramatic. Potential Clinical Applications, Benefits, and Risk: This therapeutic is anticipated to be administered to patients with NIHL via an injection to the middle ear behind the ear drum in an outpatient setting. This relatively simple procedure would result in the production of new HC and hearing restoration in a matter of weeks. A risk in RNA therapeutics is the potential of systemic effects. However, this is avoided by delivering the therapeutic directly to the ear. Injection directly to the ear is an invasive procedure. However, other drugs for ear diseases are currently delivered to the ear in this manner and the procedure is safe and easily tolerated. Projected Timeline to Achieve Expected Patient-Related Outcome: Successful completion of this project will ready our product for safety and related Investigational New Drug (IND)-enabling experiments prior to beginning FDA clinical trials. Clinical trials are projected to begin in 2020. The therapeutic should be ready for clinical use in 2026. Benefits to the Military: HEI and OPI’s therapeutic will directly benefit Warfighters and Veterans by fulfilling a need for a minimally invasive treatment for NIHL. Over half of the 4.1 million Veterans who receive benefits have auditory dis
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810017
Entities
People
- Richard Kopke
Organizations
- Hough Ear Institute
- United States Army