Key Takeaways:
A multi-center clinical trial led by researchers at Karolinska Institutet and hospitals in China delivered hearing improvements in all ten patients treated with a single AAV-OTOF gene therapy injection, with results published in Nature Medicine.
Participants, aged 1 to 24 years old with autosomal recessive deafness 9 (DFNB9) caused by OTOF gene mutations, saw average hearing thresholds improve from 106 decibels to 52 decibels at six-month follow-up, moving most from profound deafness to moderate hearing loss.
Most patients recovered some hearing within one month. A seven-year-old girl regained nearly full hearing and was having daily conversations with her mother four months after treatment.
The study, published in Nature Medicine and covered by ScienceDaily on April 3, enrolled ten patients between ages 1 and 24 at five hospitals in China. All had a genetic form of deafness or severe hearing impairment caused by mutations in the OTOF gene, which produces a protein called otoferlin that is critical for transmitting auditory signals from the ear to the brain.
Researchers used a synthetic adeno-associated virus (AAV) vector to deliver a functional copy of the OTOF gene through a single injection at the round window at the base of the cochlea. The procedure is minimally invasive.
"This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults," said Maoli Duan, consultant and docent at the Karolinska Institutet Department of Clinical Science, Intervention and Technology, and one of the study's corresponding authors.
Results were rapid. Most patients regained some hearing within one month. By six months all ten showed clear improvement, with average perceptible sound improving from 106 decibels, the level of a gas-powered lawn mower, to 52 decibels, the level of a typical conversation. Children between ages 5 and 8 responded most dramatically. One seven-year-old regained nearly full hearing and was having everyday conversations with her mother four months post-treatment.
The therapy was well-tolerated. The most common side effect was a mild decrease in neutrophils, a type of white blood cell. No serious adverse reactions were observed during 6 to 12 months of follow-up.
The OTOF gene covers only 1% to 8% of congenital hearing-loss cases. Duan said the next targets are more common deafness genes including GJB2 and TMC1. Animal studies for those targets have already returned promising results. "We are confident that patients with different kinds of genetic deafness will one day be able to receive treatment."
The therapy was developed by Otovia Therapeutics, which employs many of the researchers involved. The trial is one of several gene therapy programs for hereditary hearing loss moving toward regulatory approval. Regeneron's DB-OTO program produced similar results in a parallel study in the New England Journal of Medicine.
Over 430 million people have disabling hearing loss worldwide, and up to 60% of congenital deafness is caused by genetic factors. A single injection that moves a patient from profound deafness to everyday conversation is what transformative medicine looks like in practice.
People Also Ask
Q: How does OTOF gene therapy work? A: Researchers use a synthetic adeno-associated virus (AAV) to deliver a functional copy of the OTOF gene to hair cells in the inner ear. The gene produces otoferlin, a protein that is essential for transmitting auditory signals from the ear to the brain. The therapy is delivered as a single injection through the round window at the base of the cochlea.
Q: What is DFNB9? A: Autosomal recessive deafness 9 (DFNB9) is a form of congenital hearing loss caused by mutations in the OTOF gene. Patients are typically born with severe-to-profound hearing loss because they cannot produce functional otoferlin protein. DFNB9 accounts for 1% to 8% of congenital hearing loss cases.
Q: How much did patients' hearing improve in the trial? A: Average hearing thresholds improved from 106 decibels to 52 decibels at six-month follow-up, moving most patients from profound deafness to moderate hearing loss. Younger patients, especially those aged 5 to 8, responded most dramatically. One seven-year-old regained nearly full hearing within four months.
Q: Is gene therapy for hearing loss FDA-approved? A: No. Gene therapy for hereditary hearing loss is currently in clinical trials. Multiple programs including Regeneron's DB-OTO and Otovia Therapeutics' AAV-OTOF are advancing toward regulatory approval. The technology is not yet available as a clinical treatment in the United States.
Sources and Related Reading:
ScienceDaily (April 3, 2026): Deafness reversed: One injection restores hearing in just weeks
Karolinska Institutet: Gene therapy restored hearing in deaf patients
Nature Medicine: AAV gene therapy for autosomal recessive deafness 9
UC Irvine School of Medicine: Advancing Gene Therapy to Address Deafness
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