PNAS 2023 Cozzarelli Prize Winner for Class II: Biological Sciences

Reversal of an existing hearing loss by gene activation in Spns2 mutant mice

Elisa Martelletti, Neil J. Ingham, and Karen P. Steel

Mechanical aids can mitigate the symptoms of hearing loss, but the underlying causes are generally considered irreversible. One common form of hearing loss in mice results in the loss of electrical potential in the endolymph, which is the fluid in contact with hair cells in the cochlea. The authors of this study used a genetic mechanism in mice that lack the Spns2 gene and develop hearing loss as a result. When it was delivered early, the mechanism, which was triggered by a drug and re-instated Spns2 gene transcription, restored hearing in deaf mice. Delays in treatment resulted in diminished restoration, suggesting a critical period of reversibility. The authors suggest that the method may be used to explore the reversibility of other genetic disorders.