A British girl has had her hearing restored after becoming the first person in the world to take part in a groundbreaking new gene therapy trial.
Opal Sandy, 18 months old, was born completely deaf due to the condition auditory neuropathy, which is caused by the disruption of nerve impulses traveling from the inner ear to the brain.
Thanks to a “one and done” gene therapy being trialled in Britain and worldwide, Opal’s hearing is now almost normal – and could improve even further.
The little girl from Oxfordshire, who has a genetic form of auditory neuropathy, was treated at Addenbrooke’s Hospital, which is part of the Cambridge University Hospitals NHS Foundation Trust.
Professor Manohar Bance, an ear surgeon at the trust and lead researcher on the study, told the PA news agency that the results were “better than I had hoped or expected” and could potentially cure patients with this type of deafness.
He said: “We have results from (Opal) that are very spectacular – so close to normal hearing recovery. So we hope that it can be a possible cure.”
Auditory neuropathy can be caused by an error in the OTOF gene, which is responsible for the production of a protein called otoferlin. This allows cells in the ear to communicate with the auditory nerve.
To correct this flaw, ‘new era’ gene therapy – from biotech company Regeneron – delivers a working copy of the gene to the ear.
In Opal’s case, she received an infusion of the working gene into her right ear during surgery last September.
Her parents Jo and James, both 33, noticed improvements in her hearing within four weeks when Opal turned her head and clapped loudly.
“When she first turned around I couldn’t believe it,” Ms Sandy told PA.
‘I thought it was a fluke or a change in lighting or something that caught her attention, but I repeated it a few times.
“I picked up my phone and texted James and said, ‘I think it’s working.’ I was absolutely stunned. I thought it was a fluke.”
But there were even more impressive results to come.
About 24 weeks after the operation, in February this year, tests in Cambridge showed that Opal could also hear soft sounds, such as whispers.
“The audiologist played some sounds that she responded to and they were ridiculously soft sounds that in the real world wouldn’t get your attention during a conversation,” Ms Sandy said.
“Especially since February we have noticed that her sister (Nora) wakes her up in the morning because she is running around on the landing, or because someone rings the doorbell, interrupting her nap.
“She definitely responds more to what we would call functional sounds, rather than just sounds we use to test her.
“Last time we were told she had almost normal hearing – I think they got responses of about 25 to 30 decibels.
‘I think normal hearing is estimated at 20 decibels, so she’s not far off. Before, she had no hearing at all.”
Professor Bance said Opal’s hearing is now “almost normal”, adding: “We hope she will return to normal in the next tests.”
He added that the treatment is “a one-off therapy, so hopefully you have your treatment and then you get on with your life.”
A second child has also undergone the gene therapy treatment at Cambridge University Hospitals, with recent positive results six weeks after the operation.
The overall Phase 1/2 Chord study consists of three parts, in which three deaf children, including Opal, will receive a low dose of gene therapy in only one ear.
Another set of three children receive a high dose on one side. If this proves to be safe, more children will receive a dose in both ears at the same time.
Up to 18 young people from Britain, Spain and the US will be recruited for the trial and followed for five years.
Prof. Bance said, “My whole life, gene therapy has been ‘five years away,’ and I’ve been in practice for about 30 years.
“So for me it was almost surreal that this moment had arrived.
“It was just the fact that we’d been hearing about this for so long, and there’s been so much work, decades of work… to finally see something that actually worked in people… It was quite spectacular and a bit awe-inspiring actually. .
“It felt very special.”
Currently, cochlear implants are the gold standard treatment for auditory neuropathy.
Opal had one in her left ear while she underwent gene therapy in her right ear to ensure she could hear again as quickly as possible.
The youngster is the first patient worldwide to receive the Regeneron therapy and “as far as we know, she is the youngest in the world to have been administered so far,” said Prof. Bance.
China has also been working on targeting the same gene, with positive results, although Prof. Bance said their gene uses a different technology and a slightly different route of administration.
Doctors in Philadelphia have also reported good results with a form of gene therapy in an 11-year-old boy who had surgery after Opal.
Professor Bance said he believes the trial is “just the start of gene therapies”, adding: “It marks a new era in the treatment of deafness.
“It also supports the development of other gene therapies that could prove to make a difference in other genetically related hearing disorders, many of which are more common than auditory neuropathy.”
He said it may be a while before more children benefit from gene therapy. The treatment was not currently available on the NHS.
“What has really helped, however, is that the NHS now pays for genetic testing for hearing loss,” he said.
Opal’s surgery, which was performed under general anesthesia, was very similar to having a cochlear implant fitted, Prof. Bance continued.
“So basically we find the inner ear, we open the inner ear and we inject the treatment, in this particular case using a catheter, over 16 minutes,” he said.
“We have to make a hole in another part of the ear to let the treatment out because it has to go all the way through the ear.
“And then we just repair and seal, so it’s actually a similar approach to a cochlear implant, except we don’t put the implant in.”
Martin McLean, senior policy adviser at the National Deaf Children’s Society, welcomed the research and said it would lead to knowledge about gene therapies for deafness with a specific genetic cause.
“We would like to emphasize that, with the right support from the start, deafness should never be a barrier to happiness or fulfillment,” he said.
“As a charity we support families to make informed choices about medical technologies so they can give their deaf child the best possible start in life.”
Professor Stephen Powis, National Medical Director of NHS England, said: “This trial will transform 18-month-old Opal Sandy’s life while offering hope to many others like her, and is another example of how the NHS is leading the world in the development of genes. therapy for patients.
“The NHS has led the world in the development of a range of other innovations and therapies, and this is a very welcome addition to the work being done with life sciences organizations across England to expand the range of treatments available.”
Minister for Health and Social Care Victoria Atkins said: “I am delighted and proud of what this government-backed process has done for Opal, and what it could ultimately mean for children like them around the world.
“It marks a historic milestone in the development of a cure for this type of deafness.”