New gene therapy could prevent genetic hearing loss


Researchers at the Salk Institute have made a breakthrough that could lead to new treatments for genetic hearing loss. Gene therapy that delivers a particular protein can ensure faulty hair cells grow correctly, allowing for improved hearing.

Sensory hair cells are a vital part of our auditory system. They line the surface of the cochlea with long structures called stereocilia, which vibrate in response to sound waves and produce electrical signals that are then sent to the brain. But one form of genetic deafness arises due to a lack of a protein called EPS8, which regulates the length of these hair cells. Without it, they’re too short to work properly.

For the new study, the researchers investigated whether restoring EPS8 could help those hair cells grow to their normal length and improve hearing. Working in mice that had been engineered to lack EPS8 and, as such, were deaf, the team then experimented with using an adeno-associated virus as a vehicle to deliver the protein to the animals’ inner ears.

And sure enough, they found that the added EPS8 made the stereocilia grow longer, restoring some function to the cells that pick up lower frequency sounds.

However, there are some caveats. The treatment didn’t work in mice after a certain age, suggesting it’s important to get in early before the hair cells mature. In humans, that would require applying the gene therapy in utero, since by birth it would already be too late. But the team hopes that with further study, that window for treatment could be widened.

“EPS8 is a protein with many different functions, and we still have a lot more to uncover about it,” said Uri Manor, co-senior author of the study. “I am committed to continuing to study hearing loss and am optimistic that our work can help lead to gene therapies that restore hearing.”

Other teams have found promise in restoring hearing through gene therapy by targeting other genes. That includes regrowing either inner or outer hair cells, correcting mutations that cause them to become disorganized, or repairing age-related damage to other structures.

The new research was published in the journal Molecular Therapy – Methods & Clinical Development.

New Atlas, 11 August 2022