BRAIN-DERIVED NEUROTROPHIC FACTOR GENE-THERAPY PREVENTS SPIRAL GANGLION DEGENERATION AFTER HAIR CELL LOSS

Destruction of auditory hair cells results in the secondary degenerati on of auditory neurons, This is because of the loss of neurotrophic fa ctor support from the auditory hair cells, namely neurotrophin 3, whic h is normally produced by the inner hair cells. Both in vitro and in v ivo studies have shown that delivery of either neurotrophin 3 or brain -derived neurotrophic factor to these neurons can replace the trophic support supplied by the hair cells and prevent their degeneration. To prevent the degeneration of auditory neurons that occurs after neomyci n destruction of the auditory hair cells we used a replication defecti ve herpes simplex-1 vector (HSVbdnflac) to transfect the gene for brai n-derived neurotrophic factor into the damaged spiral ganglion, Four w eeks after the HSVbdnflac therapy we were able to detect stable functi onal production of brain-derived neurotrophic factor that supported th e survival of auditory neurons and prevented the loss of these neurons because of trophic factor deprivation-induced apoptosis.