A ‘Grasp’ Change Gene Might Result in the Remedy for Age-Associated Listening to Loss

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

Researchers at Northwestern University have uncovered a gene dubbed TBX2 that’s known as a “master regulator.” That’s because it can reprogram two types of hair cells crucial to our sense of hearing: inner and outer, according to a new study published Wednesday in the journal Nature. In mice, the researchers found that the presence of TBX2 determined whether a hair cell turned into an inner, which picks up sound vibrations; or outer, which amplifies sounds. This discovery may pave the way for tackling hearing loss —and even give insight into the evolution of human hearing.

The average adult has about 15,000 inner and outer hair cells combined inside the cochlea in each ear. These two cell types work together to help pick up the quietest of sounds and make them seem louder, Jaime García-Añoveros, a neurobiologist at Northwestern University and the study’s lead author, told The Daily Beast.

“This is a novelty that mammals have. We have the inner hair cells that when they get stimulated by sound, they communicate it to the brain,” he said. “Outer hair cells do something very unusual: They physically move. They dance in response to sound, and amplify the detection of the sound.”

Because inner and outer cells dwindle with age or die when exposed to loud noises or certain drugs like cancer drugs, research has focused on coaxing these cells to grow back. So far, there’s been limited success. Reprogrammed hair cells either tend to die quickly because they aren’t fully formed, or they just don’t become inner or outer hair cells.

Luckily, García-Añoveros and his team discovered the TBX2 gene in 2018 through a serendipitous fluke of nature. “We found a mutant in which some of the outer hair cells turned into inner hair cells. We didn’t find a mechanism, but we found a group of genes we thought could be responsible,” he said.

His team decided to play around with these genes in mice, manipulating which ones were present and functional in hair cells and seeing how this impacted a mouse’s hearing. They discovered that out of the group of potential genes, TBX2 appeared to ultimately determine whether it became an inner or an outer—so the master regulator gene could be used to replace lost or damaged hair cells of either type like a kind of switch.

“What we found in this study is that basically, if we express [TBX2] in a hair cell, we make an inner hair cell. And if we remove it, [the hair cell] becomes an outer hair cell,” said García-Añoveros.

While the study was conducted on 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. There are more roadblocks ahead, though. Even if we can reprogram hair cells in humans, that’s not a definite cure. For inner and outer hair cells to work properly, they need to be within the correct positions in the cochlea and hooked up to the body’s nervous system.

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

These findings could also lend insight into how exactly hearing evolved in mammals and why, compared to the rest of the fauna in the animal kingdom, our group of vertebrates isn’t able to regenerate hair cells.

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

It may take many years for scientists to arrive at an answer and potentially a decade or two before we could see TBX2 (and any other discoveries it spurs) applied in any way to cure hearing loss. But with science, “sometimes you’re closer to a practical application than you think,” García-Añoveros said. And now, we’ve got an upgraded genetic blueprint to guide us along the way.