Hearing breakthrough holds up in gene therapy study.

An experimental gene therapy correcting the OTOF gene produced lasting hearing improvements in a trial of 42 people, with 90% showing gains and half reaching normal hearing after 2½ years.

An experimental gene therapy that restores the OTOF gene produced durable hearing and speech-recognition gains in people with an inherited form of deafness. The study, published April 22 in Nature, was led by teams at Mass Eye and Ear, Harvard Medical School, and Fudan University and included eight trial centers in China. Participants ranged in age from nine months to 32 years and were followed for 2½ years. Researchers report ongoing follow-up and steps toward regulatory review. Key findings: - The trial enrolled 42 participants with the OTOF mutation, treated at eight centers in China. - Overall, 90% of recipients showed improved hearing; about half reached normal hearing levels by 2½ years. - Younger patients (18 and under) showed the strongest gains, while adults improved to a lesser degree. - Treatment used a neutralized virus injected into the inner-ear fluid to deliver a normal OTOF gene to cochlear hair cells; many responders heard sounds within weeks, with improvement rising over about six weeks and plateauing around 26 weeks. - No serious adverse events were reported, and no dose-related toxicity was observed across three dose groups. - Investigators said the delivery platform can be adapted to other genes (including work underway for GJB2), they will continue following participants through five years, and they are exploring regulatory steps beginning in China. Summary: The gene therapy targeting DFNB9 (OTOF mutation) resulted in lasting hearing and speech gains for most trial participants, with rapid early improvement and maintenance through 2½ years. Researchers plan continued follow-up to five years, are beginning regulatory discussions in China, and are adapting the platform to address other genetic causes of hearing loss.