Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor

Aminoglycosides are commonly used antimicrobial drugs that often have ototo xic side effects. The ototoxicity often involves permanent loss of cochlear hair cells (HCs). Neurotrophic factors have been shown to protect a variet y of tissues, including HCs, from toxic trauma. To determine if glial cell line-derived neurotrophic factor (GDNF) can protect cochlear HCs from traum a, we inoculated an adenoviral vector encoding the human GDNF gene into gui nea pig cochleae via the round window membrane 4 days prior to injection of aminoglycosides, Control groups showed little or no negative influence of the viral inoculation on cochlear structure and function, In contrast, ears that were inoculated with the GDNF vector had better hearing and fewer mis sing HCs after exposure to the ototoxins, as compared with controls. Our re sults demonstrate the feasibility of gene therapy for cochlear application and suggest that virus-mediated overexpression of GDNF may be developed as a valuable prevention against trauma-induced HC death.