The gene therapy poised to rewrite childhood deafness

Four decades have passed since cochlear implants gave infants born deaf the ability to hear. Now, as Medscape recently reported, gene therapy promises to restore natural hearing for those born with a rare form of deafness, and the discovery could lead to similar treatments for more common types of hearing loss.

The treatment, which targets a mutation in the otoferlin (OTOF) gene, has been effective in most of the tested children. The rare mutation causes hearing loss in an estimated 20 to 50 babies born in the U.S. each year. Deafness linked to OTOF mutations is a type of auditory neuropathy, a spectrum of disorders in which the inner ear can detect sound but struggles sending that information to the brain.

At least 150 genes are linked to hearing loss. The OTOF gene, however, is different because of its “unusually high safety profile,” said Daniel Choo, MD, professor and director of pediatric otolaryngology at the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center.

The results of the first clinical trials of the approach were published in 2022, and since then, five groups of researchers in the U.S., China and France have worked on drugs targeting the gene. 

Regeneron plans to file for FDA approval of its treatment by the end of the year. If it succeeds, the U.S. would be the first country to approve a gene therapy for hearing loss. 

With other gene therapies, the viral vector that delivers the treatment could leak from the target organ, turning on elsewhere in the body. But “this otoferlin gene is only turned on inside the cochlea, so even if you injected it through an IV and it ended up in your foot, there’s no way to turn it on down there,” said Choo.

Compared to children with cochlear implants only, those treated with gene therapy performed better at speech detection in noisy settings and in music perception.

But choosing gene therapy involves risk. The optimal age to acquire language is between birth and age 3, with learning becoming significantly harder after age 7, said Choo, who is the site principal investigator for Eli Lily’s upcoming clinical trial at Cincinnati Children’s.

Children can still receive a cochlear implant if gene therapy does not work — but assessing whether the therapy works in a child can take up to 18 months, complicating the decision to choose between gene therapy or a cochlear implant.

A delay in hearing improvement may affect brain development. For a 2-year-old in their prime language learning window, “that ticking clock starts calculating in the back of your head,” said Choo.

“The cochlear implant is still the best standard of care right now,” said Choo. “We can tell parents, 'this is what your kid will do in 3, 6, 9, 12 months post-implant.' We don’t have those predictable outcomes yet for gene therapy, and for some kids, it doesn’t work at all.”

Read the full Medscape article.

Featured image at top: A toddler girl wearing a Cochlear implant. Photo/iStock/satura86.