Small Molecule Therapeutics That Reactivate Cochlear Stem Cells to Generate New Hair Cells Leading to Hearing Restoration
Abstract
Objectives and Rationale: The grant objective is to prepare compounds and test them in laboratory experiments to discover a potential therapy that warrants progressing into clinical trials in humans for the treatment of noise-induced hearing loss. This therapy has the potential to regenerate sensory cells that detect sound in order to reverse hearing loss in humans. The therapy goal is to convert existing progenitor cells in the patient’s ear (cochlea) into sensory cells to restore hearing. The therapy will be delivered by a well-established medical procedure of injecting into the middle ear. The potential of this approach has been demonstrated in mice by increasing the number of sensory cells that detect sound and improving hearing after noise-induced hearing loss. Problem, Application, and Impact of Research: Hearing loss is the third most common chronic physical condition in the United States, and is more prevalent than diabetes or cancer. Sensorineural hearing loss (SNHL) accounts for about 90% of all hearing loss and is typically irreversible. SNHL has long been recognized as the primary and direct health effect of excessive noise. Occupational hearing loss, primarily caused by high noise exposure, is the most common U.S. work-related illness. Approximately 22 million U.S. workers are exposed to hazardous occupational noise. The Centers for Disease Control and Prevention (CDC) compared the prevalence of hearing impairment within nine U.S. industry sectors. Mining had the highest prevalence of workers with any hearing impairment followed by construction and manufacturing. This therapy has the potential to improve hearing across a wide range of occupational-related hearing loss including miners, construction workers, manufacturing workers, musicians, dentist, pilots, and Soldiers. Potential Clinical Applications, Benefits, and Risks: The significance of this proposal is the development of a first-in-class restorative therapy for a broad range of patients including those with hearing loss caused by noise, age, and ototoxic medicines. Improved hearing will reduce the need for hearing aids, improve the quality of life, and reduce medical disabilities. We will mitigate the standard risks of drug development by assessing ototoxicity early in development. Projected Timeline to Patient-Related Outcomes: The goal of this 2-year proposal is to progress a potential therapy into advanced testing designed to enable progression as an investigational new drug (IND) into humans. Pharmaceutical clinical development is a complex multi-phase process resulting in the combined clinical and approval time taking about 8 years on average. However, since no therapy exists, we will pursue breakthrough status with the Food and Drug Administration (FDA), which could shorten this time to approximately 5 years. Potential Benefit to Service Members, Veterans, and Family Members: Permanent hearing loss is among the top four injuries in theaters of operation of the U.S. military. Estimates are 50%-60% of situational awareness comes from hearing. Hearing allows Soldiers to detect threats in the environment and to communicate, both are critical for mission completion. Hearing loss is one of the top five reasons Soldiers cannot be redeployed. The number 1 and 2 cause of Veteran disabilities is tinnitus (ringing in ears) and hearing loss costing more than $1 billion dollars per year. Reversing hearing loss may lead to: (1) increased survival during combat operations, (2) increase ability for Soldier redeployment, (3) reduce Veteran’s disability and cost, (4) a better quality of life for Veterans, and (5) better communication with family members.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810043
Entities
People
- Will Mclean
Organizations
- Frequency Therapeutics (United States)
- United States Army