In a world-first, a British toddler has had her hearing restored in a pioneering gene therapy trial.
Doctors say this development marks a new era in treating deafness.
Before the gene therapy, Opal Sandy had profound hearing loss.
She was born with auditory neuropathy, which disrupts nerve impulses from the inner ear to the brain and can be caused by a faulty gene.
However, after receiving an infusion containing a working copy of the gene during surgery that took just 16 minutes, the 18-month-old can hear almost perfectly.
Within four weeks of having the gene therapy infusion to her right ear, Opal responded to sound, even with the cochlear implant in her left ear switched off.
Opal is the first British patient in the world and the youngest child to receive this type of treatment.
She was treated at the world-renowned Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust, which runs the CHORD trial.
The gene therapy clinical trial began in May 2023 and aims to show whether gene therapy can provide hearing for children born with auditory neuropathy.
Professor Manohar Bance, an ear surgeon at the Trust and chief investigator for the trial, said the initial results were ‘better than I hoped or expected’ and could cure patients with this type of deafness.
‘These results are spectacular and better than I expected. Gene therapy has been the future of otology and audiology for many years, and I’m so excited that it is finally here. This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss.’
Auditory neuropathy can be caused by a variation in a single gene, the OTOF gene. The gene produces a protein called otoferlin, which allows the inner hair cells in the ear to communicate with the hearing nerve.
Children with a variation in the OTOF gene often pass the newborn screening, as the hair cells are working but not talking to the nerve. This means this hearing loss is commonly detected when children are two or three years old when a speech delay is likely to be noticed.
Professor Bance added: ‘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 confuse families, as there are many reasons for delayed speech and late intervention that can impact a child’s development.
‘More than 60 years after the cochlear implant was first invented – the standard of care treatment for patients with OTOF-related hearing loss – this trial shows gene therapy could provide a future alternative. It marks a new era in the treatment of deafness. It also supports the development of other gene therapies that may make a difference in other genetic-related hearing conditions, many of which are more common than auditory neuropathy.’
Mutations in the OTOF gene can be identified by standard NHS genetic testing. Opal was identified as being at risk as her older sister has the condition; this was confirmed by a genetic test result when she was three weeks old.
Opal was given an infusion containing a harmless virus (AAV1). The virus delivers a working copy of the OTOF gene and is injected into the cochlea during surgery under general anaesthesia.
During surgery, while Opal was given gene therapy in her right ear, a cochlear implant was fitted in her left ear.
Approximately 20,000 people in the UK, Germany, France, Spain, Italy and the US are deaf due to a mutation in the OTOF gene.
More deaf children from the UK, Spain and the US are being recruited to the trial and will all be followed up for five years.
Following the procedure, Opal’s mother, Jo Sandy, said: ‘When Opal could first hear us clapping unaided it was mind-blowing – we were so happy when the clinical team confirmed at 24 weeks that her hearing was also picking up softer sounds and speech. The phrase “near normal” hearing was used, and everyone was so excited such amazing results had been achieved.’
You can watch the parents’ reaction in a video here.
