A pioneering gene therapy trial has successfully restored hearing for a British girl, making her the inaugural participant worldwide to benefit from this breakthrough treatment.
Opal Sandy, aged 18 months, was born completely deaf due to the condition of auditory neuropathy, which is caused by the disruption of nerve impulses traveling from the inner ear to the brain.
Now, thanks to a "one-and-done" gene therapy being trialed in the U.K. and worldwide, Opal's hearing is almost normal – and could even improve further.
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 chief investigator for the trial, told the PA news agency the results were "better than I hoped or expected" and may cure patients with this type of deafness.
He said: "We have results from (Opal) which are very spectacular – so close to normal hearing restoration. So we do hope it could be a potential cure."
Auditory neuropathy can be caused by a fault in the OTOF gene. This gene is responsible for making a protein called otoferlin, which 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 in her right ear during surgery last Sept.
Her parents, Jo and James, both 33, noticed improvements to her hearing in four weeks when Opal turned her head to loud clapping.
"When she first turned, I couldn't believe it," Mrs Sandy told PA.
"I thought it was a fluke or like a change in light or something that had caught her eye, but I repeated it a few times.
"I picked up my phone and texted James, 'I think it's working.' I was absolutely gobsmacked. I thought it was a fluke."
But even more impressive results were on the horizon.
Some 24 weeks after surgery, in February this year, tests in Cambridge showed Opal could hear soft sounds such as a whisper.
"The audiologist played back some of the sounds that she was responding to and they were ridiculously quiet sort of sounds that in the real world wouldn't catch your attention 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 on the landing or someone rings on the door, so her nap's cut short. She's definitely responding more to sort of what we would call functional sounds rather than sounds that we use to test her. We were told she had a near-normal hearing last time – I think they got responses at sort of 25 to 30 decibels. I think normal hearing is classed at 20 decibels, so she's not far off. Before, she had no hearing whatsoever."
Prof Bance said Opal's hearing is now "close to normal," adding: "We hope she'll get back to normal by the next testing."
He added that the treatment is "a one-and-done therapy, so hopefully you have your treatment and then you go back to your life."
A second child has also received 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 U.K., Spain, and the U.S. are being recruited for the trial and will be followed up for five years.
At the moment, the gold standard treatment for auditory neuropathy is cochlear implants.
Opal had one fitted to her left ear at the same time as she underwent gene therapy in her right ear to ensure she got hearing as soon as possible.
The youngster is the first patient globally to receive the Regeneron therapy, and "she's the youngest globally, and that's been done to date as far as we know," professor Bance said.
China has also been working on targeting the same gene, with positive results, though professor Bance said theirs uses a different technology and slightly different mode of delivery.
Medics in Philadelphia have also reported a good outcome with a type of gene therapy on an 11-year-old boy who was operated on after Opal.
Opal's surgery, which was carried out under general anesthetic, was very similar to fitting a cochlear implant, professor Bance continued.
