Toward Cochlear Therapies

Abstract

Sensorineural hearing impairment is the most common sensory disorder and a major health and socio-economic issue in industrialized countries. It is primarily due to the degeneration of mechanosensory hair cells and spiral ganglion neurons in the cochlea via complex pathophysiological mechanisms. These occur following acute and/or chronic exposure to harmful extrinsic (e.g., ototoxic drugs, noise...) and intrinsic (e.g., aging, genetic) causative factors. No clinical therapies currently exist to rescue the dying sensorineural cells or regenerate these cells once lost. Recent studies have, however, provided renewed hope, with insights into the therapeutic targets allowing the prevention and treatment of ototoxic drug- and noise-induced, age-related hearing loss as well as cochlear cell degeneration. Moreover, genetic routes involving the replacement or corrective editing of mutant sequences or defected genes are showing promise, as are cell-replacement therapies to repair damaged cells for the future restoration of hearing in deaf people. This review begins by recapitulating our current understanding of the molecular pathways that underlie cochlear sensorineural damage, as well as the survival signaling pathways that can provide endogenous protection and tissue rescue. It then guides the reader through to the recent discoveries in pharmacological, gene and cell therapy research towards hearing protection and restoration as well as their potential clinical application.

Presbycusis: An Update on Cochlear Mechanisms and Therapies

“…Mitochondrial quality control and turnover is of particular importance to cochlear sensory and neural cells because of their constant need for high levels of energy supply. Mitochondrial functionality and integrity is achieved by the quality control mechanisms of mitochondrial dynamics (fission and fusion events) and mitochondrial autophagy (mitophagy) [93].…”

Transplantation and Tracking of the Human Umbilical Cord Mesenchymal Stem Cell Labeled with Superparamagnetic Iron Oxide in Deaf Pigs

“…Sensorineural hearing loss (SNHL) has been a main hearing disorder and has seriously endangered the productivity and quality of life in our society (Wang and Puel, ). As the economy has developed, noise‐induced hearing loss (NIHL) has jumped to the first place in the incidence of nonsyndromic deafness.…”

“…Anat Rec, 303:494-505, 2020. © 2020 American Association for Anatomy Key words: human umbilical cord mesenchymal stem cells; superparamagnetic iron oxide nanoparticles; cytotoxicity; stem cell therapy; sensorineural hearing loss; noise; pig Sensorineural hearing loss (SNHL) has been a main hearing disorder and has seriously endangered the productivity and quality of life in our society (Wang and Puel, 2018). As the economy has developed, noise-induced hearing loss (NIHL) has jumped to the first place in the incidence of nonsyndromic deafness.…”

Spiral ganglion cell degeneration‐induced deafness as a consequence of reduced GATA factor activity

“…Hearing loss is the most common sensory disorder in humans, as congenital hearing loss occurs in approximately 1 affected child out of every 650 newborns (Mehl & Thomson, ). A series of studies have described that a progressive loss of the cochlear spiral ganglion cells is very frequently associated with a number of syndromic hearing loss phenotypes in human (Shibata, Budenz, Bowling, Pfingst, & Raphael, ; Wang & Puel, ). In this context, it would be of significant interest to ask whether the hearing loss in either GATA2 or GATA3 haploinsufficient humans is associated with degenerative loss of spiral ganglion cells, as we showed here in mouse models.…”