Gene therapy for deafness: are we there now?

Approximately half a billion people—5% of the world’s population—suffer from disabling hearing impairment (HI) according to the WHO (http://www.who.int/features/factfiles/deafness/en/). HI commonly hampers speech acquisition, leads to social isolation and increases risk for depression and cognitive decline. One to two per thousand children are born with disabling HI and over 50% of sensorineural HI is caused by defects in individual genes (deafness genes) of which roughly 150 have been identified so far (http://hereditaryhearingloss.org/). In case of profound hearing impairment or deafness, cochlear implants that bypass the dysfunctional or lost sensory hair cells and electrically stimulate the auditory nerve partially restore hearing. However, hearing with cochlear implants has shortcomings such as limited understanding of speech in background noise. So, there remains a major unmet medical need for improved hearing restoration (Wolf et al, 2022). Yet, despite major research efforts, a causal treatment based on pharmacology, gene therapy, or stem cells had, so far, not been clinically available. Now, this is finally changing at least for some patients: first in human trials prove the concept for inner ear gene therapy of otoferlin-related synaptic deafness.