World-first trial of gene therapy to cure children with rare type of genetic deafness begins


Published: 11 October 2023

Children born with hearing loss due to the genetic condition auditory neuropathy will be given a pioneering gene therapy in a new trial. The aim is to see if the treatment can provide them with better quality hearing compared to cochlear implants.

Auditory neuropathy is a condition where the ear can detect sound normally, but has a problem sending signals to the brain. This can be caused by a fault in the OTOF gene. The gene makes a protein called otoferlin that allows cells in the ear to communicate with the hearing nerve. Changes in this gene can cause sound transmission from the inner hair cells to the hearing nerves to be reduced. 

Gene therapy aims to deliver a working copy of the faulty OTOF gene. The treatment is given using a neutralised virus, injected into the inner ear under general anaesthetic. 

The trial is supported by NIHR Cambridge Clinical Research Facility and NIHR Cambridge Biomedical Research Centre. It will consist of three parts:

  • A starting dose of gene therapy in one ear only
  • A higher dose of gene therapy in one ear only, following proven safety of the starting dose
  • Gene therapy in both ears with the dose selected after ensuring the safety and effectiveness in parts 1 and 2

Up to 18 children from the UK, Spain and the US are being recruited to the study. The researchers will monitor the children for five years. The researchers expect initial results to be published next February.

Professor Manohar Bance is the chief investigator for the trial. He is also an ear surgeon at Cambridge University Hospitals NHS Foundation Trust. He said:

“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.

“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.”

Treating hearing loss later in life can be less effective than treating it earlier. This is because children treated later may never fully develop the ability to process the sounds of speech. If successful for OTOF related hearing loss, gene therapy treatments could offer hope for  hearing loss caused by other more common genetic conditions. 

“It’s really important that we get the first gene therapy treatment right because it will allow us to proceed to treating other genetic conditions,” added Professor Bance.

Martin McLean, Senior Policy Adviser at the National Deaf Children’s Society, said:

“The trial will help us to understand more about the effectiveness of gene therapy in improving hearing where deafness has a specific genetic cause. 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. Our role is to support families to make informed choices on whether they want to take up new treatments like this one which have the potential to mitigate the challenges their child might face.”

Around 20,000 people across the US, UK, Germany, France, Spain and Italy are thought to have auditory neuropathy due to OTOF mutations which shows the potential significance of a successful treatment. 

Addenbrooke’s Hospital in Cambridge is participating in the trial. Read more on the Cambridge University Hospitals website.


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