Gene therapy shows lasting hearing

Some babies are born with ears that detect sound but cannot pass the signal onward, like a microphone with a broken cable. A study published April 22 found a one-time gene therapy helped many of those patients hear. (nature.com) The condition is caused by mutations in OTOF, a gene that makes otoferlin, a protein inner-ear cells need to release sound messages to the auditory nerve. Without otoferlin, children with DFNB9 are born with severe-to-complete deafness even though the sound-sensing hair cells are still present. (massgeneralbrigham.org) Researchers used an adeno-associated virus, a modified virus often used as a delivery vehicle, to carry a working copy of OTOF into the inner ear. In the single-arm multicentre trial, 42 participants ages 0.8 to 32.3 years were treated at eight sites in China and followed for as long as 2.5 years. (nature.com) Hearing recovered in 90% of treated participants, and average auditory brainstem response thresholds improved from worse than 97 decibels at baseline to 42 decibels at 2.5 years. Behavioral audiometry, another hearing test, improved from worse than 96 decibels at baseline to 37 decibels at 2.5 years. (nature.com) The gains were strongest in patients ages 0.5 to 18, while adults improved less on average. Participants who improved also showed gradual gains in speech perception over time, and Harvard said more than half reached normal hearing levels by the end of follow-up. (nature.com) (news.harvard.edu) Safety was the trial’s primary endpoint in the first six weeks, and the paper reported no dose-limiting toxicities. The main grade 3 adverse event listed was decreased neutrophil count, a drop in a type of white blood cell. (nature.com) This was not the first sign the approach could work. A Nature Medicine paper published in July 2025 reported early results in 10 patients, all of whom showed hearing improvement after AAV-OTOF treatment, with the best outcomes in children ages 5 to 8. (nature.com) The new report is larger and longer than those earlier studies, which matters in gene therapy because a treatment that fades after a few months can look very different from one that holds up for years. Mass General Brigham called it the largest clinical trial yet for inherited hearing loss gene therapy and the longest follow-up reported so far. (massgeneralbrigham.org) The result still applies to a narrow slice of deafness. The authors studied autosomal recessive deafness 9, and Mass General Brigham said OTOF mutations account for about 2% to 8% of genetic cases of hearing loss present at birth. (massgeneralbrigham.org) That narrow target sits inside a much larger public-health burden: the World Health Organization says 430 million people worldwide require rehabilitation for disabling hearing loss. The closing note from this study was simpler and smaller — in some patients, a single inner-ear injection was still helping 2.5 years later. (who.int) (nature.com)