Brain-derived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss.
Destruction of auditory hair cells results in the secondary degeneration of auditory neurons. This is because of the loss of neurotrophic factor support from the auditory hair cells, namely neurotrophin 3, which is normally produced by the inner hair cells. Both in vitro and in vivo 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 neomycin destruction of the auditory hair cells we used a replication defective herpes simplex-1 vector (HSVbdnflac) to transfect the gene for brain-derived neurotrophic factor into the damaged spiral ganglion. Four weeks after the HSVbdnflac therapy we were able to detect stable functional production of brain-derived neurotrophic factor that supported the survival of auditory neurons and prevented the loss of these neurons because of trophic factor deprivation-induced apoptosis.
Department of Otolaryngology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA.
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H
Staecker
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R
Gabaizadeh
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H
Federoff
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TR
Van De Water
D000818:Animals; D000900:Anti-Bacterial Agents; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D006199:Hair Cells, Auditory, Inner / Q000293:injuries* / Q000378:metabolism*; D018259:Herpesvirus 1, Human; D051379:Mice; D008808:Mice, Inbred CBA; D009355:Neomycin; D009410:Nerve Degeneration / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D020933:Neurotrophin 3; D013136:Spiral Ganglion / Q000473:pathology*; D014162:Transfection / Q000379:methods*; D014947:Wounds and Injuries / Q000139:chemically induced
D000900:Anti-Bacterial Agents; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D009355:Neomycin