Key Takeaway: An experimental gene therapy for OTOF-related congenital deafness restored measurable hearing in about 90% (38 of 42) of participants in the largest trial to date. Improvements began within weeks, stabilized around one year, and were durable in many patients with up to two years of follow-up. No serious adverse events were reported; some temporary immune changes and mild vertigo occurred. Researchers will pursue longer follow-up, repeat-dosing studies and investigations into nonresponders.
Experimental Gene Therapy Restores Hearing in About 90% of Patients in Largest Trial to Date
(This is a stock photo and not a child treated in the trial described below.). | Credit: Xuanyu Han via Getty Images
In the largest and longest trial of its kind, an experimental gene therapy targeting OTOF-related congenital deafness produced measurable hearing gains in roughly 90% of participants. The study followed 42 people treated across eight sites in China — mostly children, plus three adults — and found improvements that emerged within weeks and generally stabilized by about one year.
Trial Overview
The open-label trial enrolled 42 participants (39 children and teens aged 9 months to 18 years, and 3 adults in their 20s and 30s). Most received the therapy in one ear because the other ear already had a cochlear implant; six participants were treated in both ears. Overall, 38 of 42 patients (about 90%) showed marked auditory improvement, while four did not respond.
How the Therapy Works
The treatment delivers functioning copies of the OTOF gene — which encodes the protein otoferlin — to inner-ear hair cells using nonpathogenic viral vectors. Otoferlin is essential for inner hair cells to convert mechanical vibrations into the neural signals the brain interprets as sound. People who inherit two defective copies of OTOF typically have severe to profound congenital hearing loss.
Outcomes and Timeline
For responding patients, hearing gains typically began within weeks and accumulated over months, then plateaued near the one-year mark. At the time of reporting, 10 participants had at least two years of follow-up: all 10 could detect normal-volume conversation (roughly 50–60 dB), and five of those could detect whisper-level sounds. The team also reported two-year data for 15 treated ears: 100% detected conversational speech and 60% detected whisper-level sounds.
“In some patients, their recovery is so good, they reach completely normal [hearing],” said study co-author Zheng-Yi Chen, associate scientist at Eaton-Peabody Laboratories, Mass Eye and Ear, and associate professor at Harvard Medical School.
Safety
No serious adverse events were reported. Some participants experienced temporary changes in specific immune-cell counts, a few had mild vertigo, and one developed transient inner-ear inflammation. Investigators described these effects as manageable within the trial context.
Different patients with OTOF-related hearing loss can carry different mutations within the gene. | Credit: Josh Hawley via Getty Images
Who Benefits Most
Children tended to show larger gains than adults, though two adults did respond well. Early analyses suggest that the health of outer hair cells — which amplify sound-induced motion in the cochlea — may influence how much hearing recovery a person can achieve. In long-standing deafness, outer hair-cell function can degrade, potentially limiting recovery; this relationship requires further study.
Speech and Development Effects
Improved hearing translated into better speech perception for many participants. Some children made notable gains in speech production after treatment, including an 11-year-old who began to say simple words after therapy despite no prior cochlear-implant use. Investigators plan to monitor rehabilitative progress to determine longer-term impacts on language development.
Limitations and Next Steps
Four participants did not respond, and the reasons remain unclear. The research team is exploring repeat dosing, longer follow-up, and expanded trials that include different patient groups. Investigators also caution that gene therapy may not be feasible in ears already implanted with a cochlear device because implantation can damage inner-ear structures, though less-damaging surgical techniques are under development.
Context and Regulatory Outlook
About 1.5 in 1,000 children are born with some form of hearing loss, and up to roughly 8% of congenital cases are linked to loss-of-function mutations in OTOF. Cochlear implants remain a highly effective and widely available treatment, but gene therapy offers the potential for a one-time biological correction that could better preserve sound quality (for example, music perception) for some patients.
The experimental therapy will continue in further trials and progress through China’s regulatory process. Study co-author Zheng-Yi Chen is a co-founder of Salubritas Therapeutics, a company developing regenerative sensory therapies; this relationship is disclosed in the report. Separately, Regeneron Pharmaceuticals has said it expects to file for U.S. approval of a different gene therapy for hereditary deafness in 2025 — a development the field is watching closely.
Note: This report summarizes experimental research and is not medical advice. Patients and caregivers should consult qualified clinicians about treatment options.
Help us improve.
