Gene therapy for genetic mutations affecting non-sensory cells in the cochlea.

Congenital hearing loss (HL) affects about 1 in every 500 infants. Among those affected more than half are caused by genetic mutations. According to the cellular sites affected by mutations in the cochlea, deafness genes could be classified into three major groups: those affecting the function of hair cells and synapses, cochlear supporting cells, and cells in the stria vascularis (SV) as well as in the lateral wall. The second and third groups account for more than half of all sensorineural hearing loss (SNHL) cases caused by genetic mutations. Current major treatment options for SNHL patients are hearing aids and cochlear implants (CIs). Hearing aids can only help patients with moderate to severe HL. Resolution of CIs is still improving and these devices are quite expensive especially when lifetime rehabilitation and maintenance costs are included. Tremendous efforts have been made to find novel treatments that are expected to restore hearing with higher-resolution and more natural quality, and to have a significantly lower cost over the lifetime of uses. Gene therapy studies have made impressive progresses in preclinical trials. This review focuses on deafness genes that affect supporting cells and cells in the SV of the cochlea. We will discuss recent progresses and remaining challenges for gene therapies targeting mutations in deafness genes belonging to this category.