by A British girl has had her hearing restored after becoming the first person in the world to take part in a ground-breaking gene therapy trial.
Opal Sandy, 18 months old, was born completely deaf due to the condition auditory neuropathy, which is caused by disruption of nerve impulses traveling from the inner ear to the brain.
Now, thanks to “one and done” gene therapy being trialled in the UK and around the world, Opal’s hearing is almost normal – and may even improve.
The little girl, from Oxfordshire, who has a genetic form of auditory neuropathy, was treated at Addenbrooke’s Hospital, which is part of Cambridge University Hospitals NHS Foundation Trust.
Professor Manohar Bance, an ear surgeon at the trust and the trial’s lead investigator, told the PA news agency that the results were “better than I expected or hoped for” and that it could help patients with the type this is their deafness to cure.
He said: “We’ve had results from (Opal) which are absolutely amazing – so close to normal hearing rehabilitation. So we hope it could be a potential cure.”
Auditory neuropathy can be caused by a defect in the OTOF gene, which is responsible for making a protein called otoferlin. This enables cells in the ear to communicate with the auditory nerve.
To overcome the defect, a “new era” gene therapy – from biotech firm Regeneron – sends a working copy of the gene to the ear.
In Opal’s case, she received an infusion containing the working gene for her right ear during surgery last September.
Her parents Jo and James, both 33, noticed her hearing had improved in four weeks when Opal turned her head to clap.
“When she first turned, I couldn’t believe it,” Mrs Sandy told PA.
“I thought it was a puke or a change in light or something that caught her eye, but I repeated it a few times.
“I picked up my phone and texted James, and said ‘I think he’s working’. I was completely gobsmacked. I thought it was a puke.”
But even more significant results were to come.
Some 24 weeks after the surgery, in February this year, tests in Cambridge showed that Opal could also hear soft whisper-like sounds.
“The audiologist played back some of the sounds she was responding to and they were very quiet sounds that wouldn’t attract your attention in real life during a conversation,” Mrs Sandy said.
“Certainly since February, we’ve noticed her sister (Nora) waking her up in the morning because she’s running around the landing, or someone knocking on the door so her nap is short.
“She’s definitely responding more to what we would call functional sounds rather than just sounds that we use to test her.
“We were told she had almost normal hearing last time – I think they got responses between 25 and 30 decibels.
“I think normal hearing is classified at 20 decibels, so it’s not far off. Before this, she had no hearing.”
Prof Bance said Opal’s hearing is now “close to normal”, adding: “Hopefully she will be back to normal by the next test.”
He added that the treatment is “a one-and-done therapy, so I hope you have your treatment and get back to your life”.
The second child received the gene therapy treatment at Cambridge University Hospitals, and positive results were seen recently, six weeks after surgery.
A complete phase 1/2 cord trial has three parts, and three deaf children, including Opal, receive a low dose of gene therapy in one ear.
A different set of three children will receive 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 young people from the UK, Spain and the US are being recruited for the trial and will be followed up for five years.
Professor Bank said: “My whole life, gene therapy is ‘five years away’, and I’ve been in practice for about 30 years.
“So for me, it was almost a blur that this moment had come.
“It was just the fact that we’ve been hearing about this for a long time, and there’s been so much work, decades of work… to finally see something that really worked in people.. .It was really amazing and a bit exciting. .
“It felt very special.”
Currently, cochlear implants are the gold standard treatment for auditory neuropathy.
Opal had one fitted in her left ear at the same time as she underwent gene therapy in her right ear, to ensure she regained hearing as soon as possible.
The teenager is the first patient in the world to receive Regeneron’s therapy and “is the youngest person in the world to have done it so far as far as we know,” Professor Bank said.
China is also working on targeting the same genes, with positive results, although Professor Bank said they use different technology and a slightly different delivery method.
Doctors in Philadelphia also reported good results with a type of gene therapy on an 11-year-old boy, who underwent surgery after Opal.
Professor Bance said he believes the trial is “just the beginning of gene therapies”, adding: “It’s a new era in the treatment of deafness.
“It also supports the development of other gene therapies that may make a difference in other genetically related hearing conditions, many of which are more common than auditory neuropathy.”
He said it may take some time for more children to benefit from gene therapy. The treatment was not currently available on the NHS.
“What has really helped is that the NHS now pays for genetic testing for hearing loss,” he said.
Opal’s surgery, which was carried out under general anaesthetic, was very similar to fitting a cochlear implant, Professor Banke continued.
“So basically, we find the inner ear and we open the inner ear and we put in the treatment, in this particular case using a catheter, over 16 minutes,” he said.
“We have to make a loose 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 close, so it’s a very similar approach to a cochlear implant, except we don’t put the implant in.”
Martin McLean, senior policy adviser at the National Association of Deaf Children, welcomed the study, saying it would lead to learning about gene therapies for deafness with a specific genetic cause.
“We want to point out that, with the right support from the start, deafness should not 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 start in life.”
Professor Stephen Powis, NHS England’s national medical director, said: “This trial will change the life of 18-month-old Opal Sandy and give hope to many others like her, and is another example of the NHS being a world leader in gene development. therapy for patients.
“The NHS is leading the world in the development of a range of other innovations and therapies, and this is a great addition to the ongoing work with life sciences organizations across England to expand the range of treatments available.”
Health and Social Care Secretary Victoria Atkins said: “I am delighted and proud of what this government-backed trial has done for Opal, and what it could ultimately do for children like her around the world .
“It’s a historic milestone as we develop a cure for this type of deafness.”
