Approaches to Treat Sensorineural Hearing Loss by Hair-Cell Regeneration: The Current State of Therapeutic Developments and Their Potential Impact on Audiological Clinical Practice

Abstract

Sensorineural hearing loss (SNHL) is typically a permanent and often progressive condition that is commonly attributed to sensory cell loss. All vertebrates except mammals can regenerate lost sensory cells. Thus, SNHL is currently only treated with hearing aids or cochlear implants. There has been extensive research to understand how regeneration occurs in nonmammals, how hair cells form during development, and what limits regeneration in maturing mammals. These studies motivated efforts to identify therapeutic interventions to regenerate hair cells as a treatment for hearing loss, with a focus on targeting supporting cells to form new sensory hair cells. The approaches include gene therapy and small molecule delivery to the inner ear. At the time of this publication, early-stage clinical trials have been conducted to test targets that have shown evidence of regenerating sensory hair cells in preclinical models. As these potential treatments move closer to a clinical reality, it will be important to understand which therapeutic option is most appropriate for a given population. It is also important to consider which audiological tests should be administered to identify hearing improvement while considering the pharmacokinetics and mechanism of a given approach. Some impacts on audiological practice could include implementing less common audiological measures as standard procedure. As devices are not capable of repairing the damaged underlying biology, hair-cell regeneration treatments could allow patients to benefit more from their devices, move from a cochlear implant candidate to a hearing aid candidate, or move a subject to not needing an assistive device. Here, we describe the background, current state, and future implications of hair-cell regeneration research.

Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish

“…Our ABR results showed that the mice exhibited high-frequency hearing deficits 4 weeks after exposure to PS-NPs, which subsequently worsened at the next 4 weeks of testing ( Figures 2D–H ). The common reason behind sensorineural hearing loss is the injury of hair cells located in the Corti organ of the cochlear auditory sensory epithelium ( Hinton et al, 2021 ). To investigate hair cell pathology caused by PS-NPs, we observed the hair cells of mice by experimental preparation of cochlear epithelia for hair cell staining, and we performed scanning electron microscopy observations of the cochlea stereocilia as well as H&E staining.…”

Unveiling the Role of Oxidative Stress in Cochlear Hair Cell Death: Prospective Phytochemical Therapeutics against Sensorineural Hearing Loss

“…Because SNHL results from permanent damage to and loss of cochlear hair cells, a fair portion of therapeutic research has set out to explore the potential of hair cell regeneration [136]. Presently, three companies have advanced preclinical data into clinical works, and these have been outlined and well described in a recent review by Hinton et al Briefly, clinical hair cell regeneration therapies primarily embrace gene therapy and small molecule inhibitor or combination approaches [137].…”

Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells

“…Emerging understanding of the mechanisms of transcription factors that induce HC differentiation (Atkinson et al, 2014 ;Bermingham et al, 1999 ;Garcia-Anoveros et al, 2022 ;Zheng and Gao, 2000 ), and potential induction for regeneration are promising, but none have produced new HCs with sustained functions (Iyer et al, 2022b ;Zine et al, 2021 ). Thus, the current treatment for hearing loss ensuing from HC loss is cochlear implants, despite the potential advantages of HC-replacement therapy (Hinton et al, 2021 ;Sullivan et al, 2020 ).…”