Abstract
Noise-induced Hearing Loss (NIHL) is a clinically significant phenomena that affects a variety of patient populations and negatively impacts quality of life. There is currently no drug approved by the Food and Drug Administration (FDA) for protection against NIHL. Repurposing an already approved FDA drug is the most cost effective and efficient. Using an in silico screen, we identified top drug hits for protective agents against NIHL. This was done via mouse model transcriptomes collected by Gratton et al., 2011, and available on the NCBI Gene Expression Omnibus (GEO) database. Afatinib was found to cover the most NIHL pathways through this method and was therefore chosen for our study. Afatinib is an FDA approved inhibitor of the epidermal growth factor receptor (EGFR) family for use against non-small cell lung carcinoma (NSCLC). A noise exposure paradigm of 100 dB for 2 hours (8-16kHz) was employed, followed by functional cochlear testing. Afatinib showed protection against hearing loss in both auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) testing. Afatinib effects on ABR results showed sexual dimorphism with only significant results for females. DPOAE results showed significant results for both males and females combined. This suggests that our in silico screen was effective and afatinib is protective against noise-induced hearing loss. Future studies include exploring the mechanism of afatinib’s protective properties, exploration of the sexually dimorphic effects of afatinib, and translation to clinical studies.