Currently, there are no treatments to reverse or prevent genetic hearing loss, which affects 1 in 500 newborns. Several gene replacement and overexpression preclinical studies targeting genetic hearing loss have shown success, as the inner ear can be accessed safely by local injection. However, all these gene therapy studies have been performed in neonatal animals, except one in the Otof gene; therefore, the suitability of the approach in the fully mature adult inner ear remains to be elucidated.
Usher syndrome is the most common cause of deaf-blindness. Mutations in the protocadherin-15 (PCDH15) gene cause Usher syndrome type 1 F (USH1F), which makes up about 3-11% of all Usher syndrome cases. As a component of tip links of the inner ear hair cells, PCDH15 binds to cadherin-23 (CDH23) to convey force from sound stimuli to the mechanosensory transduction channels.
Researchers from the University of Antwerp reported the characterization of a novel clinically relevant mouse model of DFNA9 (deafness, autosomal dominant 9), an autosomal dominant inherited disorder characterized by vestibular dysfunction and adult-onset progressive hearing loss caused by different heterozygous mutations in the COCH gene.
Wolfram syndrome is a neurodegenerative disease characterized by neurological symptoms, as well as diabetes, optic atrophy and hearing loss, among others. The WFS1 gene encodes a protein named Wolframin and it accounts for about 99% of cases, 60% of which present with hearing loss. To date, of all animal models of Wolfram syndrome developed carrying a variant or deletion of one exon of Wfs1, none mimics the early-onset hearing loss.
The CEP250 gene encodes centrosome-associated protein CEP250, involved in the formation of active centrosome components and cell cycle progression. CEP250 has been previously implicated in atypical Usher syndrome, which is characterized by early-onset hearing loss and mild retinitis pigmentosa.
To restore hearing function in patients with hearing loss or deafness, cochlear implantation is seen as the only method that works, but insertion of the electrode array may cause direct mechanical injury to the cochlea, with the subsequent loss attributed to an inflammatory response driven by proinflammatory cytokines, reactive oxygen species and apoptotic signals.
The TMEM43 gene encodes a transmembrane protein that is associated with connexin-linked function in cochlear glia-like supporting cells (GLSs), and mutations in this gene have been recently associated with hearing loss (HL).
To restore hearing function in patients with hearing loss or deafness, cochlear implantation is seen as the only method that works, but insertion of the electrode array may cause direct mechanical injury to the cochlea, with the subsequent loss attributed to an inflammatory response driven by proinflammatory cytokines, reactive oxygen species and apoptotic signals.
Decibel Therapeutics Inc. has received clearance of its clinical trial application (CTA) by the U.K.'s Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a phase I/II trial of gene therapy DB-OTO in pediatric patients with congenital hearing loss due to an otoferlin deficiency.
