A discovery revealed by Salk Institute researchers may result in novel genetic hearing loss treatments. A specific protein delivered through gene therapy can guarantee that damaged hair cells develop normally, improving hearing.
Our hearing system relies heavily on sensory hair cells. Long stereocilia, which line the surface of the cochlea, vibrate in response to sound waves and generate electrical signals later transmitted to the brain. However, an inner ear protein called EPS8 that controls the size of these outer hair cells is missing in one type of hereditary deafness. They can’t function properly without it because they are too short.
Despite the advances in technology for hearing aids and cochlear implants, the quality of hearing still cannot match that of the natural ear. The new gene therapy allows for improved hearing by delivering a certain protein that ensures faulty hair cells grow correctly.
In the latest study, the researchers looked into the possibility that replenishing EPS8 might aid in the growth of those hair cells to their standard length and enhance hearing. The scientists then tested the use of an adeno-associated virus as a delivery system for the protein to the inner ears of mice that had been genetically modified to lack EPS8 and, as a result, were deaf. Indeed, the team discovered that the additional EPS8 caused the stereocilia to lengthen, partially restoring function to the cells that detect lower-frequency sounds.
But there are some restrictions. After a particular age, the treatment was ineffective in mice, indicating the need to start treatment before the sensory cells develop. In humans, gene therapy would need to be used in utero because it would be too late to administer it after birth. However, the team believes that with more research, that window for treatment might be expanded.
The findings also suggest that other proteins involved in sensory cell development or maintenance might be potential targets for future therapies for progressive hearing loss.
Uri Manor, the study’s co-senior author, said:
“EPS8 is a protein with many different functions, and we still have much more to uncover about it. 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 discovered promise in using gene therapy to restore normal hearing by focusing on different genes. This involves rebuilding either outer or inner hair cells, reversing mutations that result in disorganization, or fixing damage brought on by aging to other structures.
The study was published in the Molecular Therapy—Methods & Clinical Development journal on September 8, 2022.
