UK hospital launches world-first gene therapy trial to cure rare deafness

UK hospital launches world-first gene therapy trial to cure rare deafness


UK doctors have launched a world-first trial to see whether gene therapy can provide hearing for children with severe to profound hearing loss due to a rare genetic condition.

The trial by Cambridge University Hospitals includes up to 18 children from the UK, Spain and the US, born with hearing loss due to auditory neuropathy — a condition caused by the disruption of nerve impulses travelling from the inner ear to the brain.

They will be followed up for five years to see the extent to which their hearing improves.

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 standard genetic testing.

About 20,000 people across the US and UK, Germany, France, Spain and Italy are thought to have auditory neuropathy due to OTOF mutations.

Children with profound hearing loss face barriers developing communication skills and may miss developmental milestones if the right support is not provided from the start.

“Children with a variation in the OTOF gene are born with severe to profound hearing loss, but they often pass the new-born hearing screening so everyone thinks they can hear. The hair cells are working, but they are not talking to the nerve,” said Professor Manohar Bance, ear surgeon at Cambridge University Hospitals.

“Gene therapy for otoferlin deficiency is the right starting point for young children because it’s among — if not the most — simple approaches for treating hearing loss, everything else should be intact and working normally.

“Although experimental, the therapy could also potentially result in better quality hearing compared to cochlear implants. But we have a short time frame to intervene because the young brain is developing so fast,” said Bance, also the chief investigator for the trial.

Intervening later in life becomes less effective as children may never fully form the ability to process the sounds of speech. If successful for OTOF-related hearing loss, gene therapy treatments could be extended to include people with hearing loss due to other more common genetic conditions.

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 during surgery under general anaesthesia. The procedure is similar to cochlear implant surgery, the current standard of care for OTOF-related hearing loss.

If the gene therapy is not effective for a child 6 months after treatment, the family can choose to receive a cochlear implant in the treated ear(s).