Who could benefit next from gene therapy that restored deaf toddler’s hearing

Thousands of children across the world who suffer from deafness and hearing loss have been given hope after a ground breaking trial allowed a British girl to hear noises for the first time.

Opal Sandy, aged 18 months, was born deaf because of auditory neuropathy, which is caused by the disruption of nerve impulses travelling from the inner ear to the brain.

Now, thanks to a “one and done” gene therapy trial being carried out in the UK and worldwide, Opal’s hearing is almost normal – and could yet improve after she became the first person in the world to take part in a groundbreaking gene therapy trial.

Opal, from Oxfordshire, was treated at Addenbrooke’s Hospital in Cambridge. The surgeon and chief investigator for the trial said he hoped she would be the first of many people to benefit from new kinds of gene therapies that can treat inner ear issues, such as hers, and potentially other kinds of hearing loss as well further down the line.

“These results are spectacular and better than I expected,” said Professor Manohar Bance, a surgeon and chief investigator for the trial.

“Gene therapy has been the future of otology and audiology for many years and I’m so excited that it is now finally here. This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss,” he said.

How does the treatment work?

Auditory neuropathy can be caused by a fault in the OTOF gene, which is responsible for making a protein called otoferlin. This enables cells in the ear to communicate with the hearing nerve.

To overcome the fault, the “new era” gene therapy – from biotech firm Regeneron – delivers a working copy of the gene to the ear.

In Opal’s case, she received an infusion containing the working gene to her right ear during surgery last September.

Opal’s surgery was very similar to fitting a cochlear implant, according to Professor Bance.

He said the inner ear (cochlea) was opened and the treatment infused using a catheter over 16 minutes.

“We have to make a release hole in another part of the ear to let the treatment out because it has to go all the way through the ear,” he said.

“And then we just repair and close up, so it’s actually a very similar approach to a cochlear implant, except we don’t put the implant in.”

Can anyone who is deaf benefit?

Children with a variation in the OTOF gene often pass the newborn screening, as the hair cells are working, but they are not talking to the nerve.

It means this hearing loss is not commonly detected until children are 2 or 3 years of age – when a delay in speech is likely to be noticed.

Professor Bance said: “We have a short time frame to intervene because of the rapid pace of brain development at this age. Delays in the diagnosis can also cause confusion for families as the many reasons for delayed speech and late intervention can impact children’s development.”

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

A second child has also received the gene therapy treatment at Cambridge University Hospitals, with positive results seen recently, six weeks after surgery.

The overall phase 1/2 Chord trial consists of three parts, with three deaf children, including Opal, receiving a low dose of gene therapy in one ear only.

A different set of three children will get a high dose on one side. Then, if that is shown to be safe, more children will receive a dose in both ears at the same time.

Up to 18 youngsters from the UK, Spain and the US are being recruited to the trial and will be followed up for five years.

Professor Stephen Powis, NHS England’s national medical director, said: “This trial will transform the life of 18-month-old Opal Sandy while offering hope to many others like her, and is another example of the NHS being a global leader in developing gene therapy for patients.”

Martin McLean, of the National Deaf Children’s Society, welcomed the study and said: “We would like to emphasise that, with the right support from the start, deafness should never be a barrier to happiness or fulfilment.”