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Current therapy for patients with hereditary absence of cochlear hair cells, who have severe or profound deafness, is restricted to cochlear implantation, a procedure that requires survival of the auditory nerve. Mouse mutations that serve as models for genetic deafness can be utilized for developing and enhancing therapies for hereditary deafness. A mouse with Pou4f3 loss of function has no hair cells and a subsequent, progressive degeneration of auditory neurons. Here we tested the influence of neurotrophin gene therapy on auditory nerve survival and peripheral sprouting in Pou4f3 mouse ears. BDNF gene transfer enhanced preservation of auditory neurons compared to control ears, in which nearly all neurons degenerated. Surviving neurons in treated ears exhibited pronounced sprouting of nerve fibers into the auditory epithelium, despite the absence of hair cells. This enhanced nerve survival and regenerative sprouting may improve the outcome of cochlear implant therapy in patients with hereditary deafness.

BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf Pou4f3 mutant mice