We are really excited about a world-first clinical 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, taking place at Addenbrooke’s Hospital in Cambridge, aims to show whether gene therapy can safely provide hearing for children 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.
Up to 18 children under the age of 18 years from three participating countries – the UK, Spain and the USA – will be included in the trial and followed for five years to see the extent to which their hearing improves.
The OTOF gene
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. Changes in the OTOF gene can be identified by standard NHS genetic testing.
About 20,000 people across the US, the UK, Germany, France, Spain and Italy, are thought to have auditory neuropathy due to variations in the OTOF gene. Children with profound hearing loss can face barriers developing communication skills and may miss developmental milestones if the right support is not provided from the start.
Professor Manohar Bance, an ear surgeon at Cambridge University Hospitals NHS Foundation Trust, and the chief investigator for the trial 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 the – 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.”
The future for hearing loss treatments
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. Professor Bance added:
“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.”
Ralph Holme, Director of Research and Insight at RNID said:
“At RNID we are committed to a future where effective treatments for hearing loss are available for those who need and want them. Gene therapies have the potential to offer long lasting and permanent treatments for hearing loss, rather than merely managing the symptoms as hearing aids do.
“This is the first treatment to try and address the underlying causes of hearing loss so it marks a real step change in how we go about treating the condition. We welcome this pioneering trial, which we hope will lead to a treatment for children with OTOF related hearing loss and pave the way towards treatments for other genetic conditions.”
How the therapy works
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.
The trial will consist of three parts, which must be done in order, with children receiving:
- A starting dose of gene therapy (DB-OTO) 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 optimal dose selected after ensuring the safety and effectiveness of DB-OTO in parts 1 and 2.
If the gene therapy is not effective for a child six months after treatment, the family can choose to receive a cochlear implant in the treated ear(s).
Find out more about the clinical trial here