Effect of Afatinib Against Noise-Induced Hearing Loss
Abstract
The World Health Organization estimates that by 2050 about 2.5 billion people will suffer from hearing loss that will be a significant health problem worldwide. Hearing loss is mainly caused by noise, platinum-based antineoplastic agents, antibiotics, and aging. Especially, hearing loss and the associated disorders are found at a greater rate in military populations than in their civilian counterparts. This comes as a result of noise exposures at potentially hazardous levels that can be found in all facets of military duty and training, day-to-day occupational duties and especially in combat. In addition, high-intensity continuous or impulse acoustic insults such as routine exposure to blasts or firearm discharge during training and/or combat cause noise-induced hearing loss (NIHL) to military personnel. As a result, hearing loss is among the leading causes of service-connected disabilities for U.S. military Veterans. Up to date, no otoprotective agents have been approved by the U.S. Food and Drug Administration (FDA) against NIHL. We have conducted a transcriptomic analysis employing data sets from two different mouse strains subjected to NIHL and identified more than 70 candidate drugs. Further analysis allowed us to narrow our group of compounds to 17, of which afatinib, an FDA-approved drug, was the top-hit candidate. Afatinib is a second-generation of tyrosine kinase inhibitors that targets epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). The goal of this proposal is to test whether afatinib can be a drug against NIHL. Our approach is to expose adult mice to a 100-dB SPL octave band noise (8kHz-16kHz) stimulus and administer afatinib before or after noise exposure. Hearing ability of the mice will be measured pre- and post-treatment and cochlear microdissection will be performed to assess inner ear morphology. The maximum nontoxic and non-ototoxic doses for afatinib will be experimentally determined by testing hearing function. Thus, successful completion of this study will lay the foundation for a direct benefit to the general population by providing a much-needed alternative to restore the auditory function after noise.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310876
Entities
People
- Jian Zuo
Organizations
- United States Army