Gene therapy trial begins in children born with rare genetic deafness

A world-first trial has launched in the UK to see whether gene therapy can provide hearing for children with severe to profound hearing loss caused by a rare genetic condition.

In children with auditory neuropathy, the ear can detect sound normally, but it is unable to communicate the signals to the brain. It can be caused by mutuation in the OTOF gene, that encodes the protein otoferlin. Otoferlin is responsible for the communication between the inner ear hair cells and the hearing nerve that travels to the brain. Some variaints in the OTOF gene disrupt this communication.

'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' said Professor Manohar Bance, professor of otology at the University of Cambridge and chief investigator for the trial. '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'.

Up to 18 children will take part in the study at Addenbrooke's Hospital in Cambridge, as well as in Spain and the USA. The therapy will aim to replace the faulty OTOF gene with a working copy. It will be delivered via a neutralised virus, injected during surgery into the cochlea, a structure within the inner ear that plays a role in hearing.

The study will first deliver a starting dose of gene therapy in only one ear. If this is proven safe, a higher dose of gene therapy will be delivered in only one ear. Finally, gene therapy will be delivered in both ears, with the optimal dose selected after ensuring the safety and effectiveness of parts one and two.

If the therapy is not effective for a child six months after treatment, they will still be eligible to receive a cochlear implant in the treated ear(s). The researchers will monitor the children and their hearing for five years; however, initial results are expected to be published in February 2024.

'This is a significant development that will be of great interest to families of deaf children whose deafness is caused by a variation in the OTOF gene. The trial will help us to understand more about the effectiveness of gene therapy in improving hearing where deafness has a specific genetic cause' said Martin McLean, senior policy advisor at the National Deaf Children's Society. 'While some families will welcome being able to access this trial, it should be emphasised that with the right support from the start, deafness is not a barrier to achievement or happiness'.