Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder.
Anissa Rym SaidiaJérôme RuelAmel BahloulBenjamin ChaixFrédéric VenailJing WangPublished in: Journal of clinical medicine (2023)
Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by an impaired transmission of sound from the cochlea to the brain. This defect can be due to a lesion or defect in the inner hair cell (IHC), IHC ribbon synapse (e.g., pre-synaptic release of glutamate), postsynaptic terminals of the spiral ganglion neurons, or demyelination and axonal loss within the auditory nerve. To date, the only clinical treatment options for ANSD are hearing aids and cochlear implantation. However, despite the advances in hearing-aid and cochlear-implant technologies, the quality of perceived sound still cannot match that of the normal ear. Recent advanced genetic diagnostics and clinical audiology made it possible to identify the precise site of a lesion and to characterize the specific disease mechanisms of ANSD, thus bringing renewed hope to the treatment or prevention of auditory neurodegeneration. Moreover, genetic routes involving the replacement or corrective editing of mutant sequences or defected genes to repair damaged cells for the future restoration of hearing in deaf people are showing promise. In this review, we provide an update on recent discoveries in the molecular pathophysiology of genetic lesions, auditory synaptopathy and neuropathy, and gene-therapy research towards hearing restoration in rodent models and in clinical trials.
Keyphrases
- hearing loss
- genome wide
- spectrum disorder
- copy number
- working memory
- gene therapy
- clinical trial
- dna methylation
- crispr cas
- spinal cord injury
- depressive symptoms
- induced apoptosis
- cell therapy
- spinal cord
- oxidative stress
- randomized controlled trial
- signaling pathway
- cell death
- neuropathic pain
- gene expression
- big data
- cell cycle arrest
- transcription factor
- open label
- quality improvement
- artificial intelligence
- optic nerve
- replacement therapy
- genetic diversity
- subarachnoid hemorrhage
- bioinformatics analysis