Have you heard? Viral-mediated gene therapy restores hearing

Abstract

Genetic loss of VGLUT3 in cochlear inner hair cells results in profound deafness. In this issue of Neuron, Akil et al. (2012) show that AAV-mediated introduction of wild-type VGLUT3 in the genetically deaf mouse cochlea results in significantly improved hearing.

Figure 1

Cartoon showing the organ of Corti inner and outer hair cells. The typical inner hair cell connects to auditory nerve fibers and depolarizes them by releasing glutamate upon sound activation. To the right of the hair cell are schematic drawings of the ribbon synapse as seen by electron microscopy. In Vglut3 mutant mice VGLUT3 is absent, the ribbon and neurotransmitter vesicles appear pathological (the ribbon is flat and vesicles are elongated), and hearing is absent (the musical notes depict hearing ability or lack thereof). In Vglut3 mutant mice treated with AAV1-mediated Vglut3 gene transfer, VGLUT3 can be detected in inner hair cells, and both the ribbon and the vesicles more closely resemble the normal morphology. Mice treated with AAV-Vglut3 exhibit normal hearing thresholds as measure by electrophysiology and also exhibit hearing using behavioural assays.