Hearing loss caused by noise exposure is a major unmet medical need in our society, affecting over 600 million people worldwide. The need is especially critical to military Service Members who encounter noise damage as part of their daily training and in combat. To date, no drugs have been approved by the U.S. Food and Drug Administration (FDA) to treat hearing loss; development of a drug to treat the condition would be a significant contribution to human health. We recently conducted unbiased screens of large number of FDA-approved drugs that can be administered to humans (1,300 drugs) for cisplatin-induced cell-death protection in an inner-ear cell line and identified a top candidate drug, Tamiflu (Oseltamivir Phosphate), with a good safety profile. Tamiflu is an oral, widely used, antiviral drug to treat the flu in humans two weeks and older who have had common flu-like symptoms for 48 hours or less. In our studies, Tamiflu protected mouse cochlear explants against hair cell death induced by cisplatin damage (a mimic insult to noise), and significant protective effects were demonstrated in adult mice against noise-induced hearing loss. We measured significant protection effects of the drug when the mice received the drug 45 minutes before noise exposure and, importantly, also 24 hours post noise exposure (24-28 dB protection). Protection was measured by two functional hearing tests in mice and by restoration of the connection between the nerve fibers and hair cells in the inner ear required for hearing. Thus, we aim to rapidly repurpose Tamiflu for oral delivery to humans to protect from noise-induced hearing loss. In this proposal, we will test in mice different regimens of drug administration and various noise levels to optimize the drug Tamiflu for clinical studies in humans. The study can lead to identification of a new cellular target by which Tamiflu protects the inner ear cells from noise damage, and to an FDA-approved oral drug for hearing protection and reduction of hearing damage after noise exposure to benefit military service personnel and the general population.
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