Single-injection OTOF gene therapy improved hearing in all 10 trial patients
A single-arm trial in Nature Medicine found that a one-time OTOF gene therapy injection improved hearing in all 10 patients with congenital deafness. Some responded within a month, and no serious adverse events were observed.
A single gene therapy injection improved hearing in all 10 patients with a rare form of congenital deafness caused by mutations in the OTOF gene. Published in Nature Medicine, the single-arm trial found that some patients began responding to sound within one month, with average hearing thresholds improving from around 106 decibels to approximately 52 decibels by six months.
The study involved 10 patients aged between 1 and 24 years. Researchers used a synthetic adeno-associated virus (AAV) to deliver a functional copy of the OTOF gene directly into the inner ear through the round window membrane of the cochlea.
The OTOF gene is responsible for producing otoferlin, a protein essential for transmitting sound signals from the inner ear to the brain. Without otoferlin, the auditory system cannot properly relay signals, resulting in profound deafness from birth, while in this subtype the physical structures of the inner ear remain intact.
Once inside the cochlea, the virus delivers the genetic blueprint needed to produce otoferlin. This restores the ability of inner ear hair cells to transmit sound signals to the brain, effectively reactivating a pathway that had been non-functional since birth.
Most participants began to regain some hearing within one month of treatment, with consistent improvements observed across all patients by the six-month mark. One seven-year-old child regained near-normal hearing and was able to hold everyday conversations with her mother within four months.
The most dramatic responses were observed in younger children, particularly those aged five to eight. The therapy also produced meaningful improvements in teenagers and adults.
The therapy was found to be safe and well tolerated across all participants. The most commonly reported side effect was a temporary reduction in neutrophils, and no serious adverse events were observed during the follow-up period of six to twelve months.
The current therapy targets OTOF-related deafness, which accounts for approximately 1 to 8 per cent of cases of congenital hearing loss. Researchers are expanding work to more common genes such as GJB2 and TMC1, though these are more complicated to treat and early animal studies have shown promising results.