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.
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.
Otoferlin is a calcium sensor protein critical for the transmission of the signal from inner hair cells (IHCs) to the spiral ganglion neurons (SGNs), and it is encoded by the OTOF gene. Pathogenic biallelic loss of function variations in OTOF result in failure of synaptic transmission, causing autosomal recessive deafness 9 (DFNB9), which is a congenital severe-to-profound auditory neuropathy.
Hearing loss related to aging is mostly predicted by the degree of loss of outer hair cells. Investigators from Acousia Therapeutics GmbH have tested the novel Kv7.4 channel activator ACOU-082 in mice.
Otosclerosis affects about 0.3% of population and it is among the most common cause of conductive hearing loss. Otosclerosis is highly familial, with positive family history reported in about 50% to 60% of cases. The disease is characterized by pathologic remodeling of the bone encasing the inner ear (otic capsule).
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.