Long-Term Success of Gene Therapy for Inherited Deafness Confirmed in Major Trials

An experimental gene therapy for a rare form of inherited deafness has restored hearing in 90% of participants, with benefits lasting up to 2.5 years, according to the largest and longest follow-up trial of its kind published in Nature on April 22, 2026.

The multicenter study, co-led by researchers from Mass General Brigham and the Eye & ENT Hospital of Fudan University, treated 42 individuals born with complete hearing loss due to mutations in the OTOF gene, which causes autosomal recessive deafness 9 (DFNB9). All participants received a one-time intravenous infusion of the gene therapy, designed to deliver a functional copy of the OTOF gene to inner ear cells.

Results showed marked improvements in hearing across the cohort, with children demonstrating greater gains than adults. In some cases, hearing recovered to completely normal levels. Zheng-Yi Chen, DPhil, associate scientist at Mass Eye and Ear and corresponding author of the study, described the outcomes as remarkable, noting that for many patients, the restoration of hearing also enabled the development and use of speech.

The therapy targets the otoferlin protein, essential for transmitting sound signals from the inner ear hair cells to the auditory nerve. Mutations in the OTOF gene prevent this protein from functioning, resulting in profound congenital deafness. By correcting the genetic defect, the treatment aims to restore the biological mechanism of hearing rather than relying on assistive devices.

Improvements in hearing were observed to progress over time and plateaued by approximately one year post-treatment, after which benefits remained stable through the 2.5-year follow-up period—the longest duration reported to date for any gene therapy trial targeting inherited hearing loss.

While the trial primarily included children, three adults aged up to 32 also received the therapy, with two showing positive responses. Researchers noted that although pediatric patients experienced more robust recovery, the findings support the potential for adult benefit as well.

The study builds on earlier research, including a smaller trial published two years prior, and aligns with findings from other groups investigating similar gene therapies for various forms of genetic deafness. Experts suggest that early intervention may yield the best outcomes, reinforcing growing interest in newborn screening for genetic hearing loss to enable treatment during critical windows of language development.

To date, no gene therapy for hearing loss has received regulatory approval, but the current results position the OTOF-targeted approach as a leading candidate for future authorization. Scientists emphasize that while the therapy shows promise, it applies only to a specific genetic subset of deafness—those caused by OTOF mutations—and does not address other forms of hearing impairment.

The research team continues to monitor participants for long-term safety and durability of effect, with plans to expand trials to additional sites and refine delivery methods. As gene-editing technologies advance, this approach may inform broader strategies for treating sensory disorders rooted in single-gene defects.