An experimental gene therapy gave a deaf child the ability to hear, her family and investigators for a clinical trial say.
Opal Sandy, the girl, received an injection of DB-OTO, Regeneron’s gene therapy, in her ear when she was 11 months old. Her hearing was assessed as normal within six months.
“When Opal could first hear us clapping unaided it was mind-blowing,” Jo Sandy, the girl’s mother, said in a statement released by the UK’s National Health Service (NHS).
Opal can now hear her parents and responds with words such as “Dada,” according to her parents.
“Providing the full complexity and spectrum of sound in children born with profound genetic deafness is a phenomenon I did not expect to see in my lifetime,” Dr. Lawrence Lustig, chair of Columbia University’s Department of Otolaryngology and one of the trial investigators, said in a statement.
Opal was born with genetic deafness from mutations of the otoferlin gene. About one in every 500 children are born in the United States with little or no ability to hear, and genetic changes like variants of the otoferlin gene are one cause.
Variants in the gene inhibit the production of a protein necessary for communication between the inner ear and the auditory nerve. The problem can be partially rectified with hearing aids or cochlear implants.
“It was our ultimate goal for Opal to hear all the speech sounds. It’s already making a difference to our day-to-day lives, like at bath-time or swimming, when Opal can’t wear her cochlear implant,” James Sandy, Opal’s father, said.
The DB-OTO is aimed at restoring the full spectrum of sound to people with mutated otoferlin gene. It’s given as an intracochlear injection into one ear, or administered directly to the inner ear. A phase 1/2 clinical trial testing the gene therapy started in 2023, enrolling children in the United States, the United Kingdom, and Spain.
Regeneron is based in New York state.
The goals of the non-randomized, open-label trial include learning more about the safety and efficacy of the therapy. Investigators planned to measure the incidence and severity of adverse events experienced by the children, as well as changes in hearing following receipt of the injection. Some participants are receiving a single injection in one ear while others are receiving simultaneous injections in both ears.
DB-OTO uses a virus that’s been modified so that it does not pose a threat to humans. It “aims to deliver a working copy to replace the faulty otoferlin gene,” according to Regeneron.
When Opal was first tested, she had no detectable hearing, according to a presentation given to the American Society of Gene and Cell Therapy on Wednesday. Hearing ability was detected four weeks after the injection and continued until being measured as normal around five months later, Regeneron said in a press release.
No hearing improvement was detected in Opal’s untreated ear.
Investigators also reported that a second child who received an injection at age 4 showed improved hearing six weeks after receiving DB-OTO. The hearing is measured through several tests, including pure tone audiometry, which involves evaluating reaction toward a sound that’s emitted at different decibel levels.
“These impressive results showcase the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related deafness, and we are excited to see how this translates into an individual’s development, especially since early intervention is associated with better outcomes for speech development,” Dr. Lustig said.
Investigators said there were no adverse events among participants that were related to the therapy.
The trial is enrolling additional participants as Regeneron seeks further testing of its product.
“These results are spectacular and better than I expected. Gene therapy has been the future in otology and audiology for many years and I’m so excited that it is now finally here,” Manohar Bance, an ear surgeon with NHS, said in a statement. “This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss.”
