Spiral ganglion neurons are protected from degeneration by GDNF gene therapy

Perceptual benefits: from the cochlear prosthesis are related to the quanti ty and quality of the patient's auditory nerve population. Multiple neurotr ophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have been shown to have important roles in the survival of inner ear audito ry neurons, including protection of deafferented spiral ganglion cells (SGC s). In this study, GDNF gene therapy was tested for its ability to enhance survival of SGCs after aminoglycoside/diuretic-induced insult that eliminat ed the inner hair cells. The GDNF transgene was delivered by adenoviral vec tors. Similar vectors with a reporter gene (lacZ) insert served as controls . Four or seven days after bilateral deafening, 5 mul of an adenoviral susp ension (Ad-GDNF or Ad-lacZ) or an artificial perilymph was injected into th e left scala tympani of guinea pigs. Animals were sacrificed 28 days after deafening and their inner ears prepared for SGC counts. Adenoviral-mediated GDNF transgene expression enhanced SGC survival in the left (viral-treated ) deafened ears. This observation suggests that GDNF is one of the survival factors in the inner ear and may help maintain the auditory neurons after insult. Application of GDNF and other survival factors via gene therapy has great potential for inducing survival of auditory neurons following hair c ell loss.