Zebrafish Screen for Ototoxic and Otoprotective Agents

DESCRIPTION (provided by applicant): This SBIR aims to develop a quantitative in vivo zebrafish hair cell assay that can be used to predict drug induced ototoxicity in humans and to identify potential otoprotective agents. Zebrafish is a good animal model since neuromast hair cells in zebrafish, located in stereotypical positions in the head and trunk region, are structurally and functionally similar to the inner ear hair cells in mammals. Human hair cells can be damaged by infection, aging, genetic disease, noise or treatment with drugs, including anti-cancer drugs and antibiotics. Drug-induced ototoxicity can ultimately lead to sensory hair cell death, causing hearing loss and vestibular disorders. Although hearing aids are useful for some patients with hearing loss, there is no effective therapy. Current therapeutic strategies include application of growth factors and other agents to promote cell survival, and systemic application of drugs to prevent activation of programmed cell death. The proposed zebrafish assay will facilitate development of protective treatments to minimize ototoxic side effects and increase the clinical utility of current medications.