A ‘major’ transgene could lead to a cure for age-related hearing loss

Next time you listen to Taylor Swift’s favorite song, you can thank the thousands of tiny cells inside an organ in your inner ear called the cochlea. They’re called hair cells – not because it’s actually hair, but because they look like hair under a microscope. They are responsible for collecting and relaying sounds to the brain. As we age, hair cells are damaged or destroyed, leading to age-related hearing loss. For years, scientists have been trying to figure out how to reverse these effects, and now, they may have hit gold.

Researchers at Northwestern University discovered a gene called TBX2, known as a “master regulator”. That’s because it can reprogram two types of hair cells important to our hearing: internal and external, according to a new study published Wednesday in the journal Nature. In mice, the researchers found that the presence of TBX2 determines whether a hair cell turns inward, which receives acoustic vibrations; or outside, which amplifies the sound. This discovery could pave the way to addressing hearing loss — and even provide insight into the development of human hearing.

The average adult has about 15,000 combined inner and outer hair cells inside the cochlea in each ear. Jaime García-Añoveros, a neurobiologist at Northwestern University and lead author of the study, says the two types of cells work together to help pick up the quietest sounds and make them sound loud. than.

“This is a novelty that mammals have. We have hair cells inside that, when they are stimulated by sound, they communicate to the brain,” he said. “The outer hair cells do something very unusual: They move physically. They dance in response to sounds and amplify their ability to detect sounds. “

Because internal and external cells decline with age or die when exposed to loud noise or certain drugs such as cancer drugs, research has focused on encouraging these cells to grow. develop again. So far, there has been little success. Reprogrammed hair cells tend to die quickly because they are not fully formed or they do not become internal or external hair cells.

Fortunately, García-Añoveros and his team discovered the TBX2 gene in 2018 through a fluke that happened to occur in the wild. “We found a mutant in which some outer hair cells turn into inner hair cells. He said:

His team decided to test these genes in mice, control which genes are present and active in hair cells, and see how this affects the mice’s hearing. They found that out of a pool of potential genes, TBX2 seems to ultimately determine whether it becomes an internal or an extrinsic gene — so the key regulatory gene could be used to replace lost hair cells. or damaged, like some kind of switch.

“What we found in this study is that basically, if we show [TBX2] In the hair cell, we make an inner hair cell. And if we delete it, [the hair cell] becomes an outer hair cell,” says García-Añoveros.

While the study was done in mice, García-Añoveros believes this genetic mechanism is similar in humans and will be a gamechanger in improving our understanding of hearing loss and how to reverse it. . However, there are many hurdles ahead. Even if we could reprogram human hair cells, that would not be a cure-all. For the inner and outer hair cells to function properly, they need to be located in the correct locations in the cochlea and connected to the body’s nervous system.

“I won’t say we have solved the problem and can now start trying [in humans],” said García-Añoveros. “You’ll have to see if they restore hearing in mice and if not, we have to ask why they don’t? Is it because they are not properly positioned or is it because they are not properly connected to the brain? The good news is that we now have the tools to study this.”

The findings may also provide insight into how exactly hearing develops in mammals and why, compared with the rest of animals in the animal kingdom, the vertebrate group Ours can’t regenerate hair cells.

“The evolution of hearing is important because it allows mammals to hear exceptionally well. But it’s also surprising that [humans] lose the ability to regenerate [their hair cells],” said García-Añoveros. “Birds can do it, and so can reptiles, fish, and amphibians. Why mammals, who have better hearing, why can’t we reproduce it naturally? ”

It could be years before scientists come up with an answer, and it’s likely to be a decade or two before we see TBX2 (and any other discoveries it spurred) applied. in any way to cure hearing loss. But with science, “sometimes you are closer to a practical application than you think,” says García-Añoveros. And now, we’ve got an upgraded genetic blueprint to guide us along the way.