Genetic Tweaks Are Restoring Hearing In Animals, Raising Hopes For People

Jul 8, 2015
Originally published on June 7, 2016 12:14 pm

Researchers have taken another step toward reversing deafness using gene therapy.

The latest success involves mice with an inherited form of deafness, a team reports Wednesday in the journal Science Translational Medicine. And a similar approach is already being tried in people with hearing loss caused by damage to cells in the inner ear.

"I'd say we are very close" to having gene therapies that can restore hearing loss from a wide range of causes, says Dr. Tobias Moser, a professor of auditory neuroscience at the University of Göttingen in Germany. Moser wrote an article accompanying the mouse study.

The new study is the result of an effort to help children with hearing loss caused by genetic defects, says co-author Jeffrey Holt, a researcher at Harvard and Boston Children's Hospital whose work is supported by the Bertarelli Foundation. In the U.S. alone, thousands of children are born each year with inherited hearing loss.

But gene therapies could eventually allow many of them to hear, Holt says. "A baby who is born deaf could have their genome sequenced," he says. "If we identify the specific gene that's causing the deafness then you could tailor a precision treatment, hopefully restoring function."

Holt and his team, including lead author Charles Askew, have been studying genes that affect hearing. And they've focused on a gene called TMC1.

Normally this gene allows cells in the inner ear to convert sounds into electrical signals that are sent to the brain, Holt says. But when the gene is mutated, he says, this doesn't happen.

"Once we realized we had this deafness gene we began thinking about how we might be able to restore function in these patients with genetic hearing loss," Holt says.

Their idea was to use gene therapy to replace mutated TMC1 genes with genes that functioned correctly. And when the team tried this in mice, "the deaf mice began to jump" when they heard a loud sound.

Electrical signals in the brain confirmed that the mice were no longer deaf. But the treatment didn't fully restore hearing, and still needs some tweaks, Holt says.

"It would be premature to say this is ready for the clinic," Holt says. "But I am optimistic that in the not too distant future some of this really could make a difference in people's lives."

The big question now is not whether gene therapy for inherited deafness will work, but whether there will be enough money to pay for it, says Moser. That's because there are dozens of different genetic mutations that can affect hearing and each one may need its own customized treatment, he says.

"If you think how much it will cost to really go through all the clinical trials until you actually have [Food and Drug Administration] approval, this will I fear really limit the chances to put this into practice," he says.

On the other hand, countries including the U.S. have already proved willing to spend a lot to restore hearing, says Hinrich Staecker, an otolaryngologist and researcher at the University of Kansas Medical Center. "People consider it a very effective use of funds to put two cochlear implants in a child," he says. "So you're looking at an intervention to make a child hear again at a cost of $120,000 or so.

Staecker is one of the scientists conducting the first study attempting to use gene therapy to restore hearing in people. It's funded by the drug company Novartis and involves adults who have lost most of their hearing because of damage to hair cells, the receptors in the inner ear that detect sound. The most common reasons for this damage are toxic medications and exposure to very loud sounds.

The therapy is designed to deliver a gene to the inner ear that generates new hair cells. That approach worked in animals, but it's too soon to say whether it will also work in people, Staecker says.

The good news so far is that the treatment hasn't caused any health problems, Staecker says. That's been a major concern ever since a teenager died in an early experiment using gene therapy

"We have not had any safety issues with the trial," Staecker says. "So I think the whole idea of using gene therapy for hearing loss is probably something that we will be able to do."

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ROBERT SIEGEL, HOST:

Researchers have taken another step toward reversing deafness using gene therapy. Their latest success involves mice with an inherited form of deafness. And as NPR's Jon Hamilton reports, a trial of gene therapy for people with hearing loss is already underway.

JON HAMILTON, BYLINE: Each year thousands of babies in the U.S. are born with hearing loss caused by genetic defects. Jeffrey Holt, a researcher at Harvard and Boston Children's Hospital, foresees a day when their hearing could be restored.

JEFFREY HOLT: A baby who is born deaf could have their genome sequenced. If we identify the specific gene that's causing the deafness, then you could tailor a precision treatment.

HAMILTON: So Holt and his team have been studying genes that effect hearing. And they focused on a gene called TMC1. Holt says normally this gene allows cells in the inner ear to convert sounds into electrical signals that are sent to the brain. But when the gene is mutated, he says, this doesn't happen.

HOLT: Once we realized that we had this deafness gene, we began thinking about how we might be able to restore function in these patients with genetic hearing loss.

HAMILTON: The idea was to use gene therapy to replace mutated TMC1 genes with genes that function correctly. Holt says the team tried this in mice, and it worked.

HOLT: A normal wild-type mouse, if you play a loud sound, will jump. A deaf mouse doesn't do that at all. But after using our gene therapy approach, the deaf mice began to jump.

HAMILTON: Holt says the treatment, reported in the journal Science Translational Medicine, didn't fully restore hearing in the mice and still needs some tweaks.

HOLT: I want to be cautiously optimistic. I don't want to give deaf patients false hope. But I am optimistic that in the not-too-distant future some of this really could make a difference in people's lives.

HAMILTON: Many other scientists share Holt's cautious optimism.

TOBIAS MOSER: Well, I'd say we are very close.

HAMILTON: Tobias Moser is a professor of auditory neuroscience at the University of Gottingen in Germany. Moser says the big question is not whether gene therapy for inherited deafness will work but whether there will be enough money to pay for it. He says lots of genetic mutations can effect hearing and each one may need a different treatment.

MOSER: If you think how much it will cost to really go through all the clinical trials until you actually have FDA approval, this will, I fear, limit the chances to really put this into practice.

HAMILTON: Hinrich Staecker at the University of Kansas Medical Center agrees that precision medicine is expensive. But he says society places a very high value on hearing.

HINRICH STAECKER: People consider it a very effective use of funds to put two cochlear implants in a child. So you're looking at an intervention to make a child hear again at $120,000 or so.

HAMILTON: Staecker is part of the first study using gene therapy on people with hearing loss. He says the study, funded by the drug company Novartis, involves people who have damage to hair cells, the receptors in the inner ear that detect sound. These cells can be harmed by certain medications and exposure to very loud sounds.

STAECKER: Our genetic switch, which is a gene called ATOH1, is designed to generate new hair cells.

HAMILTON: The genetic switch worked in animals. Staecker says it's too soon to say whether it will also work in people. But he says the good news so far is that the treatment hasn't caused any health problems, a real concern with treatments that alter a person's genes.

STAECKER: We have not had any safety issues with the trial. So I think the whole idea of using gene therapy for hearing loss is probably something that we will be able to do.

HAMILTON: Staecker says the study will take at least another year to complete. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.