Researchers Test Gene Therapy Designed to Improve Hearing

A gene therapy developed with the help of Harvard Medical School researchers restored hearing in 90 percent of patients with a rare form of inherited deafness, according to a study published last month.

The study, published in Nature, was co-authored by Harvard Medical School professor Zheng-Yi Chen, who collaborated with researchers from several Chinese universities to design and conduct trials at eight medical centers in China.

The treatment was most effective among patients younger than 18, though adults also saw improvements. By the end of the two-and-a-half-year study, half of all participants had reached normal hearing levels.

The therapy targets OTOF, a gene that helps transmit signals between hair cells in the inner ear and the neurons that carry sound to the brain. While only about 50 babies in the United States are born each year with hearing loss linked to OTOF mutations, the gene has become a leading target for genetic hearing restoration.

Unlike many other forms of genetic hearing loss, which cause ear cells to deteriorate over time, hearing loss caused by OTOF mutations — known as otoferlin deafness — leaves the inner ear’s hair cells and sensory neurons intact. That makes the condition a particularly promising candidate for gene therapy, Chen said.

“All they need is this missing molecule,” Chen said. “So we give the molecule back.”

Still, finding enough patients for a full trial has been difficult. Because otoferlin deafness is so rare, Chen said researchers often have to recruit globally. Even in places where the condition is more common — including Spain, Korea, and parts of China — case numbers remain low.

The study included 42 participants between nine months and 32 years old. Some patients, Chen said, went from being unable to hear an explosion to being able to hear a whisper.

Patients began regaining hearing within four weeks of injection, with improvements continuing for up to a year before reaching their peak. Those gains persisted one, two, and two-and-a-half years after treatment.

Some patients treated as late as age 11 were also able to develop limited speech ability — a result Chen called unexpected.

“That’s actually very surprising,” Chen said, “because the general view is, by that age, you have no capability to develop speech anymore.”

Delivering the treatment posed another challenge. Researchers used a small, neutralized virus to carry the OTOF gene into hair cells in the inner ear, allowing the body to produce the missing protein. But the therapeutic must be injected into the fluid of the inner ear, requiring delicate surgery to reach the cochlea, which is embedded in the densest bone in the body.

Before the therapy can reach patients outside a clinical trial, it will need regulatory approval in China — and, if researchers choose to expand access, in other countries. Still, Chen described the results as a “paradigm shift,” saying they could open the door to gene therapies for other forms of congenital hearing loss.

“The other very important implication of the study is the over 150-200 genetic deafness genes we know of,” Chen said. “We had no way of treating those patients prior to this one. But with this success, suddenly they open a door.”

The study was published in Nature on April 22 — one day before the Food and Drug Administration granted accelerated approval to a similar treatment targeting OTOF mutations developed by the biopharmaceutical company Regeneron. Chen said he expects to see similar therapeutics targeting other hearing loss-related genes emerge in the next year.

“We can start seeing new treatment coming on board for many different types of patients. It’s very meaningful for all of us who work in the field because we want to help to transform people’s lives, make their lives much better,” Chen said.

Article originally appeared on The Harvard Crimson