A new study has documented “considerable improvement” in all 10 patients who received one injection of gene therapy for congenital deafness or severe hearing impairment in a trial in China.
Researchers said the therapy was safe and well tolerated, and a six-month follow-up after treatment showed the average volume of perceptible sound (pure-tone-average hearing level) improved from 106 decibels at baseline to 52 dB in all participants.
“This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults,” said Dr Maoli Duan, one of the study’s corresponding authors.
Researchers said the study showed gene therapy could improve hearing in children and adults with congenital deafness or severe hearing impairment.
The participants, aged 18 months to 23 were treated at five hospitals in China. All had a genetic form of deafness or severe hearing impairment caused by mutations in a gene called OTOF. These mutations cause a deficiency of the protein otoferlin, which plays a critical part in transmitting auditory signals from the ear to the brain.
The gene therapy used a synthetic adeno-associated virus (AAV) to deliver a functional version of the OTOF gene to the inner ear via a single injection through a membrane at the base of the cochlea called the round window.
“Therapeutic effect was rapid, taking one month to achieve most of the overall hearing improvement,” the authors reported in Nature Medicine on 2 July 2025.
Best results in children
An age-dependent therapeutic effect was observed, with those aged between five and eight, responding best to the treatment.
One seven-year-old girl quickly recovered almost all her hearing and was able to have daily conversations with her mother four months afterwards. But the therapy also proved effective in adults, they said.
“Smaller studies in China have previously shown positive results in children, but this is the first time that the method has been tested in teenagers and adults too,” Dr Duan said.
“Hearing was greatly improved in many of the participants, which can have a profound effect on their life quality. We will now be following these patients to see how lasting the effect is.”
Dr Duan is a consultant and docent at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden. The study involved researchers from the institute and was conducted in collaboration with hospitals and universities in China.
The researchers said results showed the treatment was safe and well-tolerated.
There were 162 grade I/II adverse events (mild to bothersome) with the most common adverse reaction being a reduction in the number of neutrophils, a type of white blood cell. No serious adverse reactions were reported in the follow-up period of six to 12 months.
Primary and secondary endpoints
The primary endpoints were safety and tolerability within five years, and secondary endpoints assessed auditory function.
Apart from improving pure-tone-average hearing level from baseline, other secondary endpoints showed similar improvements, researchers reported.
These included the average click auditory brainstem response (ABR) threshold, the tone-burst ABR threshold and the auditory steady-state response (101 ± 1 to 48 ± 26 dB, 91 ± 4 to 57 ± 19 dB and 80 ± 14 to 64 ± 21 dB, respectively).
“On an individual level, click and tone-burst ABR thresholds, but not the auditory steady-state response, reliably predicted the behavioural pure-tone-average thresholds after four months,” researchers said.
“These preliminary results show that AAV-OTOF was safe and well tolerated in patients ranging from toddlerhood to adulthood. The trial remains ongoing and requires extended follow-up to confirm the long-term safety and efficacy.”
Other genes being studied
Dr Duan said: “OTOF is just the beginning. 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. We are confident that patients with different kinds of genetic deafness will one day be able to receive treatment.”
The study, a single-arm experimental trial, was conducted with several institutions including Zhongda Hospital, Southeast University, China.
Several Chinese research programs financed the study with Otovia Therapeutics Inc., the company that developed the gene therapy and which employs five of the 21 researchers involved in the study.
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