Genetic modification may prevent hereditary hearing loss

Hereditary hearing loss can worsen over time and lead to premature deafness. In a new study, a Yale-led research team successfully applied genetic modification to delay inherited hearing loss in mice.

Led by professor of pathology and genetics Gerald S. Shadel, the collaborative research team genetically altered mice to develop a model of hearing loss caused by a defect in mitochondria (specialized compartments within cells).

Hearing loss in these mice was found to involve dysfunction in specialized tissues in the inner ear. The research team determined that activation of a stress-response enzyme called AMPK triggered this dysfunction.

Genetically reducing AMPK activity (by knocking out one of its genes) had no impact on mice with normal hearing, but delayed or prevented hereditary hearing loss in the deafness-model mice.

While more research is needed, the study results point to possible strategies for preventing or treating deafness associated with mitochondrial dysfunction and aging in people.

''This opens the possibility for intervention in humans based on inhibiting AMPK, which is already a drug target for several diseases,'' stated Dr. Shadel.

The study was published online by The American Journal of Pathology. Other Yale authors include Sharen E. McKay, Wayne Yan, Jessica Nouws, Maximilian J. Thormann, Abdul Khan, Joseph Santos-Sacchi, and Lei Song. Co-author Nuno Raimundo is from the University Medical Center Goettingen in Germany.