Toddler born deaf can hear after world-first gene therapy
When Opal Sandy was four days old, doctors told her parents that she was completely deaf. But 18 months later Opal delights in hearing cutlery slammed on a table or the sounds of tinkling on a piano.
She was the first person in the world to take part in a revolutionary trial using gene therapy to treat a type of genetic deafness. Her mother said she was “gobsmacked” that Opal’s hearing was almost normal after treatment at Addenbrooke’s Hospital in Cambridge.
Opal, of Eynsham, Oxfordshire, was born deaf due to a condition called auditory neuropathy, when nerve impulses that transport sounds to the brain are disrupted. It can be caused by a fault in the OTOF gene, which produces a protein that enables cells in the ear to communicate with the hearing nerve.
The trial, led by Cambridge University Hospitals NHS Foundation Trust, is using the latest gene therapy to deliver a working copy of the gene to cells in the ear, replacing the faulty ones.
Opal received an infusion produced by Regeneron, an American biotech company, in her right ear during surgery last September. Three weeks later she responded to loud noises for the first time. Her mother, Jo Sandy, said she was “testing quite loud sounds like clapping, wooden spoons on saucepans” when Opal turned her head.
“When she first turned, I couldn’t believe it,” she added. “I thought it was a fluke or … something that had caught her eye. But I repeated it a few times.”
Sandy said she texted her husband, James, to tell him she thought it was working. “I was absolutely gobsmacked,” she added. “I thought it was a fluke. I couldn’t really believe it.”
Tests last February, 24 weeks after the surgery, showed Opal’s hearing had continued to improve and she could hear soft sounds such as a whisper.
In the past six weeks she has started to speak. Her mother said: “She’s good at all your common first baby words, so ‘daddy’ is a favourite.”
Sandy, 33, a secondary school geography teacher, and her husband, also 33, who works in car manufacturing, also have a five-year old daughter, Nora, who has the same genetic form of auditory neuropathy. She wears cochlear implants — a type of hearing aid that is the current gold standard treatment — but requires intense speech and language therapy.
Sandy said the sisters now liked “seeing who can make the most noise”. She added: “Nora got into music quite recently and [Opal] likes to … do little dances in the kitchen. So they like dancing together.”
Professor Manohar Bance, an ear surgeon who is chief investigator for the trial, said the results were “spectacular” and raised hopes of a cure. He added that the treatment was “a one-and-done therapy, so hopefully you have your treatment and then you go back to your life”.
Opal is the first patient to receive the Regeneron therapy in a trial that will recruit up to 18 youngsters from the UK, Spain and the US. Bance said he believed the trial was “just the beginning” of gene therapies.
Opal and her older sister, Nora, like playing at who can make the most noise
ANDREW MATTHEWS/PA
He added: “It marks a new era in the treatment for deafness. It also supports the development of other gene therapies that may prove to make a difference in other genetic-related hearing conditions, many of which are more common than auditory neuropathy.”
A second child has received the treatment at Cambridge University Hospitals, with positive results seen six weeks after surgery.
The gene therapy used in the trial is called DB-OTO and is specifically for children with OTOF mutations. A modified and harmless virus is used to carry the working gene, enabling the material to be delivered to specific cells.
Bance said Opal’s surgery under general anaesthetic was similar to fitting a cochlear implant. He said: “We open the inner ear and we infuse the treatment — in this particular case using a catheter — over 16 minutes.
Jo Sandy texted her husband James, right, when she realised Opal’s treatment was working
ANDREW MATTHEWS/PA WIRE
“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. And then we just repair and close up.”
During the surgery Opal had a cochlear implant fitted to her left ear to ensure she could hear as soon as possible.
The 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. Another set of three children will get a high dose on one side. If that is shown to be safe, further children will get a dose in both ears at the same time.
About 20,000 people across the US, UK, Germany, France, Spain and Italy are thought to have auditory neuropathy due to OTOF mutations.
Results from the Chord study were presented on Wednesday to the American Society of Gene and Cell Therapy conference in the US city of Baltimore.
Martin McLean, senior policy adviser at the National Deaf Children’s Society, said: “Many families will welcome these developments, and we look forward to learning about the long-term outcomes for the children treated.
“This trial will teach us more about the effectiveness of gene therapy in those cases where deafness has a specific genetic cause. We would like to emphasise that, with the right support from the start, deafness should never be a barrier to happiness or fulfilment. As a charity, we support families to make informed choices about medical technologies, so that they can give their deaf child the best possible start in life.”
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