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TL;DR
This preclinical study used viral gene therapy to express a gain-of-function acetylcholine receptor in cochlear hair cells of mice lacking efferent inhibition, which reduced temporary hearing loss following acoustic trauma.
Molecular Therapy. Methods & Clinical Development · 8 authors, 3 centres
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This preclinical study used viral gene therapy to express a gain-of-function acetylcholine receptor in cochlear hair cells of mice lacking efferent inhibition, which reduced temporary hearing loss following acoustic trauma.
The study investigated whether enhancing efferent cochlear inhibition could protect the inner ear from acoustic trauma. Researchers used viral transduction to express a gain-of-function nicotinic acetylcholine receptor (α9L9′T) in the cochlear hair cells of mice genetically lacking efferent inhibition (α9-null). The presence of the transgene at synaptic sites was visualized in excised tissue. Following viral treatment, acoustic trauma-induced temporary hearing loss, measured via auditory brain-stem response (ABR) at 1 day post-trauma, was reduced compared to controls. Specifically, both the ABR threshold shift (indicative of outer hair cell amplification) and the evoked-response amplitude (indicative of afferent signaling) were protected. The results provide proof-of-principle that a gene therapy approach to strengthen efferent feedback could be a potential strategy for preventing noise-induced hearing loss. Limitations include the need to test efficacy in wild-type mice, assess long-term expression and behavioral hearing, and evaluate potential vestibular side effects.