Is -Associated Hearing Loss (DFNB93) a Gene Therapy Target? Preclinical Progress and Patient Registry.

modulates presynaptic Ca1.3 Ca channel function in inner hair cells (IHCs) and is required for indefatigable synaptic sound encoding. Biallelic variants in are associated with non-syndromic hearing loss (DFNB93). Otoacoustic emissions have been observed in an Italian family with a homozygous variant, indicating preservation of outer hair cell-mediated cochlear amplification. Hence, DFNB93 belongs to the hearing disorders caused by impairment of IHC synapses, termed auditory synaptopathy. DFNB93 mouse models have recapitulated findings and demonstrated that lack of CaBP2 impairs synaptic sound encoding by enhanced steady-state inactivation of Ca1.3 Ca channels. Furthermore, preclinical studies have demonstrated feasibility of gene therapy. As growing evidence from clinical trials confirms synaptopathies as promising therapeutic targets for hearing restoration, ranks highly among the candidate genes for virus-mediated gene therapy to restore hearing. This perspective summarizes the preclinical gene replacement studies for hereditary hearing loss and outlines the characteristics that make genetic targets ideal for therapy development. It reviews the current literature on human studies, pre-clinical therapy development, and introduces a patient registry that aims to support research involvement with the patient community. We conclude with a preview of the next steps toward gene therapy clinical trials.