First-ever gene therapy trial to cure form of deafness begins

A world-first trial of a gene therapy to cure a form of deafness has begun, potentially heralding a revolution in the treatment of hearing loss.

Up to 18 children from the UK, Spain, and the US are being recruited to the study, which aims to transform treatment of auditory neuropathy, a condition caused by the disruption of nerve impulses traveling from the inner ear to the brain.

Participants will be monitored for five years to gauge whether their hearing improves, with initial results expected to be published next February.

Professor Manohar Bance, an ear surgeon at Cambridge University Hospitals NHS Foundation Trust who is leading the trial in the UK, said a decision by the NHS last year to start funding genetic testing for hearing loss had been crucial in “changing the whole landscape” for the development of gene therapies.

Gene therapies now held remarkable promise to restore hearing, he suggested. “It’s the dawn of a new era,” he added.

Auditory neuropathy can be due to a variation in a single gene—known as the OTOF gene—which produces a protein called otoferlin. This protein typically allows the inner hair cells in the ear to communicate with the hearing nerve.

Mutations in the OTOF gene can be identified by genetic testing. However, Bance said it was a condition often missed when newborn babies were screened for potential hearing problems. “This is one of the few conditions where everything works except the transmission between the hair cells and the nerve. So everything else looks fine when you test it, but they can’t hear anything. So these poor kids’ [difficulties] end up being missed,” Bance added.

The new gene therapy aims to deliver a working copy of the faulty OTOF gene using a modified, non-pathogenic virus. It will be delivered via an injection into the cochlea under general anesthetic.

The gold standard treatment for the condition is currently cochlear implants, but they have limitations. They do not filter out background noise in complex hearing environments, such as when multiple people are speaking, often making it difficult to participate in group conversations or to enjoy music.

Bence estimates that about 20,000 people across the US and five European countries—the UK, Germany, France, Spain, and Italy—have auditory neuropathy due to OTOF mutations, underlining the potential significance of a successful treatment.

He said his foundation trust in Cambridge had in recent months established genetic hearing loss clinics, bringing together clinical geneticists and clinicians. The development had allowed them to identify “all kinds of genetic hearing losses that we weren’t really aware of before.”

There was already precedent for using gene therapy for other conditions, he noted, citing Zolgensma, a licensed treatment for spinal muscular atrophy in young children, and a treatment under development for a form of blindness.

However, he acknowledged that resource constraints might pose a barrier to the adoption of gene treatment in poorer nations despite the fact that, if proved effective, it had much to offer in regions such as Africa that sometimes lacked the facilities to provide continuing maintenance for cochlear implants.

“If it works, it’s ‘one and done’” but the cost to health systems “is something that worries me,” he added, noting that gene therapies could be priced in “the million dollar range” per patient. However, he hoped that “economies of scale” as the technology developed further would ultimately allow them to be provided more cheaply.

Ralph Holme, director of research and insight at RNID, which supports people with hearing impairments, said that if the trial proved successful “we could have a transformational opportunity to allow these children to be able to hear, which is really exciting.”