A person's hearing can be damaged by loud noise, aging and even certain medications, with little recourse beyond a hearing aid or cochlear implant.
But now, UCSF scientists have achieved a breakthrough in understanding what is happening in the inner ear during hearing loss, laying the groundwork for preventing deafness.
The research, published on Dec. 22, 2023, in the Journal of Clinical Investigation Insight, links animal studies on hearing loss with a rare type of inherited deafness in humans. In both cases, mutations to the TMTC4 gene trigger a molecular domino effect known as the unfolded protein response (UPR), leading to the death of hair cells in the inner ear.
Intriguingly, hearing loss from loud noise exposure or drugs such as cisplatin, a common form of chemotherapy, also stems from activation of the UPR in hair cells, suggesting that the UPR may underly several different forms of deafness.
There are several drugs that block the UPR - and stop hearing loss - in laboratory animals. The new findings make a stronger case for testing these drugs in people who are at risk of losing their hearing, according to the researchers.
"Millions of American adults lose their hearing due to noise exposure or aging each year, but it's been a mystery what was going wrong," said Dylan Chan, MD, PhD, co-senior author on the paper and director of the Children's Communication Center (CCC) in the UCSF Department of Otolaryngology. "We now have solid evidence that TMTC4 is a human deafness gene and that the UPR is a genuine target for preventing deafness."
