Gene Therapy after Hearing Loss

Le résumé fourni par la source

Purpose: The most common cause of deafness is due to the loss of cochlear hair cells and a degeneration of the sensory epithelia. The degeneration of the sensory epithelia leads to a degeneration of the auditory nerves, which are the targets for cochlear implant stimulation. This work aims to prevent the degeneration of the auditory nerves and regenerate the cochlear hair cells. Methods: Adenoviral vectors which have been modified to encode for brain derived neurotrophic factor and neurotrophin-3 or the transcription factor Atoh1 were injected into the cochlear scala media of deafened guinea pigs (n=5 for each group). Cochleae were examined after 3, 7, 11 or 24 weeks of treatment. Results: After a single inoculation of neurotrophin gene therapy there was a significantly greater density of auditory nerves at all time points examined in the region most proximal to the viral injection when compared to the contralateral cochlea (p<0.05). There was also evidence for localised resprouting towards neurotrophin producing cells. The introduction of the transcription factor, Atoh1, was shown to cause transduced cells to transdifferentiate towards a hair-cell phenotype when examined after 3 weeks. Conclusions: Neurotrophin gene therapy is able to promote an increase in auditory nerve survival for at least 6 months in the deafened guinea pig. Moreover, Atoh1 gene therapy promotes the regeneration of cochlear hair cells, cells once thought to be lost forever, by causing transdifferentiation of supporting cells towards a hair cell phenotype.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.