Modulating the Cochlear Proteostasis Network to Prevent Hidden Hearing Loss
Abstract
The goal of this project is to develop a noninvasive therapeutic strategy to protect US Service members from noise-induced hearing loss (NIHL). Recently, it was unexpectedly found that many US Service members suffer from NIHL despite having normal hearing tests. This phenomenon, now called hidden hearing loss, represents a major health crisis for both the US Service members and the American public at large. Our objective is to test the therapeutic potential of four molecular targets identified in our preliminary studies. We will assess target engagement with complementary strategies and investigate the safety and potency of our proposed therapeutic strategies. NIHL is one of the most common occupational illnesses in the US, affecting 12% of adolescents and 17% of adults. Currently, surgery cannot correct NIHL and there are no effective medicines available. NIHL is caused by damage to cells within the inner ear that detect sound and transmit the information to the brain. Exposure to intense levels of sound is common while serving in the military and can cause temporary or permanent hearing loss. In our preliminary studies, we identified a panel of biological molecules within the inner ear that have altered levels immediately after noise exposure in mice. I hypothesize that these molecules may represent key therapeutic targets for the prevention of NIHL in humans. We also identified a small panel of molecules that are specifically involved in the recovery process that occurs days and a few weeks after noise exposure. In this project, we will use commercially available dietary supplements and FDA-approved drugs to modulate the level or activity of these targets and test if they can prevent hidden hearing loss in mice. The benefit of this strategy is twofold. First, by using previously FDA-approved drugs there will be only minimal clinical risks since these supplements and molecules have already been deemed as safe for human consumption. Second, because they are already available and have been previously characterized there should be little delay in repurposing them for NIHL. Thus, for at least one of our strategies, the projected timeline to achieve a patient-related outcome is expected to be very short. To maximize the potential impact of our therapeutic strategies we will test whether they can be used to both effectively prevent NIHL or accelerate the recovery process after overexposure to damaging levels of sound. I expect that this project will contribute to advancing the field of hearing restoration research in several ways. First, it will provide a new understanding of the molecular pathways and networks involved with NIHL. This is an essential first step toward treating NIHL and we are well suited to perform these experiments based on our publication record of accomplishment. Second, testing five different therapeutic strategies to prevent or treat hidden hearing loss will also advance our understanding of previously discovered pathways and allow us to explore completely new targets in the context of NIHL. I expect that this project will increase the operational performance and quality of life of US Service members and the American public at large by reducing the incidence and severity of NIHL. By preventing hidden hearing loss, we expect that our Service members will be better able to communicate on the battlefield, perform their duties, complete their missions, and return home with normal hearing. The potential benefits of my proposed research are not limited to US Service members; if successful, our regimen will be used to treat or prevent hidden hearing loss in the American public at large.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910627
Entities
People
- Jeffrey N Savas
Organizations
- Northwestern University
- United States Army