Repurposing Oseltamivir, a Commonly Prescribed Influenza Antiviral, for the Prevention of Noise- and Cisplatin-Induced Hearing Loss

Hearing loss affects up to 10% of people worldwide. Yet currently, there is only one FDA-approved drug for its prevention in a subgroup of cisplatin-treated pediatric patients. Here, we performed an unbiased screen of 1,300 FDA-approved drugs for protection against cisplatin-induced cell death in an inner ear cell line, and identified oseltamivir phosphate (brand name Tamiflu), a common influenza antiviral drug, as a top candidate. Oseltamivir phosphate was found to be otoprotective by oral delivery in multiple established cisplatin and noise exposure mouse models. The drug conferred permanent hearing protection of 15-25 decibel Sound-Pressure Level (dB SPL) for both female and male mice. In mice, oseltamivir treatment reduced outer hair cell death after cisplatin treatment and mitigated cochlear synaptopathy after noise exposure. We showed that a potential binding protein, ERK1/2, associated with inflammation, was activated with cisplatin treatment and reduced with oseltamivir cotreatment in cochlear explants. Importantly, we also associated oseltamivir treatment with a significant reduction in the number of infiltrating immune cells to the cochleae in mice after noise exposure,suggesting an anti-inflammatory mechanism of action. Our results support oseltamivir, a widespread drug for influenza with low side effects, as a promising otoprotective therapeutic candidate in both cisplatin chemotherapy and traumatic noise exposure.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2025

Author dc:creator

• Longsworth, Emma Sailor

Advisor dc:contributor.advisor

• Teitz, Tal

• acoustic trauma
• cisplatin
• hearing loss
• noise exposure
• oseltamivir

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Repository record dc:identifier.uri

https://cdr.creighton.edu/handle/10504/157688

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/157688