More and more children are hearing thanks to advances in gene therapy for profound deafness

There are few things more heartwarming than videos of deaf children gaining the ability to hear, showing them happily turning their heads to the sound of their parents’ voices and dancing happily to newly discovered music. Thanks to recent advances in gene therapy, more and more children are experiencing these sweet, triumphant moments, without the need for hearing aids or cochlear implants.

At the American Society for Gene & Cell Therapy annual conference in Baltimore this week, researchers showed several of these videos to their expert audience. On Wednesday, Larry Lustig, an otolaryngologist at Columbia University, presented data from clinical trials of two children with profound deafness — the most severe type of deafness — who are now able to hear to normal levels after receiving experimental gene therapy. One of the children was 11 months old at the time of treatment, making him the youngest child in the world to receive gene therapy for genetic deafness.

On Thursday, Yilai Shu, an otolaryngologist at Fudan University in Shanghai, presented a one-year progress report on six children treated in the first human gene therapy trial. Five of the six people regained their hearing.

This trial, like the one presented by Lustig, involved treating only one ear in all children – a safety measure for such early trials. But Shu and his colleagues have already moved to treating both ears, or bilateral treatment. After providing a progress report on the first trial, Shu presented the first unpublished data on five additional patients who participated in the first-in-human trial of bilateral treatment. All had bilateral hearing restoration and improvement in speech perception.

“The ability to provide the full complexity and spectrum of sound to children born with profound genetic deafness is a phenomenon I did not expect to see in my lifetime,” Lustig said in a statement.

Jump point

Shu and Lustig’s essays are distinct but the treatments are, in broad outline, similar. Both aim to restore hearing loss caused by mutations in the OTOF gene, which codes for the protein otoferlin. Normally, otoferlin is a protein essential for transmitting sound signals to the brain, specifically playing a key role in synaptic transmission between the inner hair cells of the ear and the auditory nerve. Using gutted adeno-associated viruses as vectors for gene delivery, the therapies deliver a functional version of the OTOF gene to the inner ear. Once in the ear, the gene can be translated into functional otoferlin, restoring auditory signaling.

In the trial presented by Lustig, both patients saw gradual improvement in their hearing as the otoferlin protein accumulated after treatment. For the 11-month-old, normal hearing levels were restored within 24 weeks of treatment. For the second patient, a 4-year-old child, improvements were detected during a six-week assessment. In the trial presented by Shu, children began to see hearing improvements at assessments at three and four weeks. Children will continue to be monitored in a future that has some uncertainties. It is unknown whether they will, at some point in their lives, need additional treatments to maintain their hearing. In mice, at least, the treatment lasts the animals’ entire lives, but they only live a few years.

“We hope it lasts a long time,” Lustig said Wednesday. But “we don’t know what’s going to happen and we don’t know if we can do a second dose. But, I guess, probably, at some point it will have to be done.”

For now, the treatment is considered low-hanging fruit in the burgeoning field of gene therapy because it targets a serious disease caused by recessive mutations in a single gene. Mutations in otoferlin lead to a very specific type of deafness called auditory neuropathy, in which the ear fails to send signals to the brain but functions perfectly otherwise. It is an ultra-rare form of deafness that affects 1 to 8% of people with deafness worldwide. In the United States, only about 30 to 50 people are born with this type of hearing loss each year.

However, Lustig calls this a “jump point.” Now that researchers have shown that this gene therapy can work, “this will really spark, we hope, the development of gene therapy for more common types of deafness,” he said.