Scientists have discovered that genetic mutations that cause a molecular domino effect that causes hearing loss mirror mechanisms involved in noise- and age-related hearing loss. They believe that by inhibiting the key role of this mechanism, they could instead protect all ears from damage and prevent hearing loss.
Researchers at the University of California, San Francisco (UCSF) have discovered specific and important commonalities between animal and human studies. TMTC4 The genetic mutation turns on a mechanism known as the unfolded protein response (UPR), which destroys hair cells in the inner ear.
Like all mammals, humans have two types of cochlear hair cells, inner and outer, that play different but important roles in sensory communication. Hair cells in the inner ear, of which there are approximately 3,500 at birth, convert sound vibrations in the cochlear fluid into electrical signals that are transmitted to the brain, but once damaged they cannot be regenerated.
By targeting the activation of the UPR in hair cells, which occurs both due to genetic mutations, lifestyle and age-related hearing loss, and drugs such as chemotherapy treatment cisplatin, researchers are They have discovered that they have the potential to protect these valuable sensors from death.
“Each year, millions of American adults lose hearing due to noise or aging, but the cause of the problem remains a mystery,” said co-author Dr. Dylan Chan, director of the Department of Otolaryngology at UCSF. says. “We now have solid evidence of that. TMTC4 is a human hearing loss gene, and the UPR is a true target for preventing hearing loss. ”
When exposed to stimuli such as loud music or stadium crowds, the noise can bend and destroy hair cells. Researchers believe this activates the UPR, essentially causing the cell to self-destruct, causing permanent damage.
For this study, Chan partnered with Elliott Sher, who has conducted previous research. TMTC4 Mutations in young patients and mouse models. Researchers found that genetic mutations in both humans and mice cause hair cells to self-destruct, resulting in rapidly progressive hearing loss typically seen with age or noise-induced damage. In all cases, hair cells were filled with excess calcium, resulting in dysfunction of signals, including the UPR.
However, a drug developed at UCSF to reverse memory deficits in traumatic brain injury inhibits part of the UPR and inhibits inner hair cells, even when mice are exposed to potentially harmful loud noises. It has also been shown to protect against damage.
The research team hopes to develop a non-invasive drug that reduces activation of the UPR, protecting hair cells from damage and, in turn, preventing hearing loss.
Previous research from the University of Iowa also highlighted the potential to prevent hearing loss at the molecular level by targeting modulation of chemical and electrical mechanisms in the inner ear.
“If there is a way to prevent hair cells from dying, that would be a way to prevent hearing loss,” Chan said.
This study Clinical Research Insights Journal.
Source: University of California, San Francisco
