A groundbreaking clinical trial has demonstrated that gene therapy can successfully restore hearing in children and adults with congenital deafness. All ten participants, aged 1.5 to 24 years, showed hearing improvements following treatment, with optimal results observed in 5- to 8-year-olds.
docent at the Department of Clinical
Science, Intervention and Technology,
Karolinska Institutet (© Ulf Sirborn)
Researchers from Karolinska Institutet and collaborating institutions in China have achieved a significant breakthrough in treating genetic hearing loss, with a new gene therapy showing promise across a broader age range than previously demonstrated. The study, published in Nature Medicine on 2 July 2025, represents the first multicentre clinical trial of gene therapy for deafness to include adult participants.
Revolutionary treatment targets genetic cause
The therapy addresses autosomal recessive deafness 9 (DFNB9), a condition caused by mutations in the OTOF gene. These mutations lead to a deficiency of otoferlin, a protein essential for transmitting auditory signals from the ear to the brain. The treatment involves using a synthetic adeno-associated virus (AAV) called Anc80L65 to deliver a functional version of the OTOF gene directly to the inner ear through a single injection via the round window membrane.
“This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults,” says Dr Maoli Duan, consultant and docent at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and one of the study’s corresponding authors.
Rapid and sustained improvements
The results were remarkably swift, with the majority of patients recovering some hearing within just one month of treatment. At the six-month follow-up, all participants demonstrated considerable hearing improvement, with average sound perception thresholds improving from 106 decibels to 52 decibels.
One particularly striking case involved a seven-year-old girl who rapidly recovered almost all her hearing and was able to hold daily conversations with her mother just four months after treatment. The study authors noted in their discussion that “the effect of gene therapy is rapid, taking 1 month to achieve 62% in PTA [pure-tone average] and 78% in TB-ABR [tone-burst auditory brainstem response] of the total improved hearing at 6 months.”
Age-dependent therapeutic effects
A significant finding was the age-dependent nature of the treatment’s effectiveness. The researchers observed that “the most improvement (>80 dB) occurred in participants aged between 5 and 8 years old, whereas participants younger and older than this age range showed much less improvement.”
This discovery has important implications for treatment timing. “OTOF is just the beginning,” says Dr Duan. “We and other researchers are expanding our work to other, more common genes that cause deafness, such as GJB2 and TMC1. These are more complicated to treat, but animal studies have so far returned promising results.”
Safety profile and future directions
The treatment demonstrated excellent safety and tolerability. The most common adverse reaction was a reduction in neutrophils, a type of white blood cell, but no serious adverse reactions were reported during the 6-12 month follow-up period.
The study included ten participants across five hospitals in China, with ages ranging from 1.5 to 23.9 years. Seven participants received gene therapy in one ear due to unilateral cochlear implantation, while three received treatment in both ears.
The authors concluded that “we found that a single injection of AAV-OTOF is well tolerated and safe, effectively improving hearing in DFNB9 patients of various ages.” However, they emphasised that “future larger trials are needed to validate these findings.”
Expanding therapeutic horizons
This research builds upon earlier studies that had been limited to paediatric populations.
The inclusion of adolescents and adults significantly expands the potential patient population for genetic hearing loss treatments. The study’s multicentre design and longer follow-up periods provide robust evidence for the therapy’s efficacy and safety profile.
The findings suggest that gene therapy could offer hope to the millions of people
worldwide affected by genetic hearing loss, marking a pivotal moment in the treatment
of congenital deafness.
Reference:
Qi, J., Zhang, L., Lu, L., et. al. (2025). AAV gene therapy for autosomal recessive deafness 9: a single-arm trial. Nature Medicine. https://doi.org/10.1038/s41591-025-03773-w
