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bioRxiv · 10.1101/2023.05.02.539081

Reversal of an existing hearing loss in mutant mice

Martelletti, E.·Ingham, N. J.·Steel, K. P.
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Abstract

Hearing loss is highly heterogeneous but one common form involves a failure to maintain the local ionic environment of the sensory hair cells reflected in a reduced endocochlear potential. We used a genetic approach to ask if this type of pathology can be reversed, using the Spns2tm1a mouse mutant known to show this defect. By activating Spns2 gene transcription at different ages after the onset of hearing loss we found that an existing auditory impairment can be reversed to give close to normal thresholds for an Auditory Brainstem Response (ABR), at least at low to mid stimulus frequencies. Delaying the activation of Spns2 led to less effective recovery of ABR thresholds suggesting there is a critical period for intervention. Early activation of Spns2 not only led to improvement in auditory function but also to protection of sensory hair cells from secondary degeneration. The genetic approach we have used to establish that this type of hearing loss is in principle reversible could be extended to many other diseases using available mouse resources. Significance statementNeurological diseases are often thought to be irreversible, including hearing loss. In this study we found that one type of hearing loss can be reversed as long as the treatment is delivered within a critical period early in disease progression. This result is a proof-of-concept that hearing loss not only can be avoided but also may be reversed. This genetic approach can be used for a wide range of diseases using existing mouse resources.

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Martelletti, E., Ingham, N. J., Steel, K. P.. 2023-05-03. Reversal of an existing hearing loss in mutant mice. https://doi.org/10.1101/2023.05.02.539081

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