In a collaborative effort between researchers at Karolinska Institutet and several Chinese hospitals and universities, gene therapy was administered to ten patients, leading to noticeable hearing improvement across all participants. The therapy was found to be safe and well-tolerated.

“This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults,” stated Maoli Duan, one of the study’s corresponding authors and a consultant and docent at the Karolinska Institutet’s Department of Clinical Science, Intervention and Technology.

The participants, aged between 1 and 24 years, were treated at five hospitals in China. Each had hearing loss caused by mutations in the OTOF gene, which affects the production of otoferlin—a protein essential for transmitting sound signals from the ear to the brain.

Rapid Onset of Improvement

A functional OTOF gene was injected once into the inner ear through the round window, a membrane at the base of the cochlea, using a synthetic adeno-associated virus (AAV).

Within a month of treatment, the majority of patients showed improvements in their hearing. After six months, all participants showed substantial progress, with the average detectable sound level improving from 106 decibels to 52.

Best Outcomes in Younger Patients

Children, particularly those aged five to eight, responded most positively. One notable case involved a seven-year-old girl who regained nearly all her hearing within four months and could engage in daily conversations with her mother.

“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 noted. “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.”

Safety and Future Potential

The treatment was generally well-tolerated. During the six to twelve months of follow-up, no significant negative effects were recorded, however the most frequent side effect was a brief decrease in neutrophils, a kind of white blood cell.

“OTOF is just the beginning,” said 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. We are confident that patients with different kinds of genetic deafness will one day be able to receive treatment.”

The research was supported by various Chinese research programs and Otovia Therapeutics Inc., the company behind the gene therapy, which also employs many of the study’s contributors. Further details, including conflicts of interest, can be found in the published article.

Original Publication
Authors: Jieyu Qi, Liyan Zhang, Ling Lu, Fangzhi Tan, Cheng Cheng, Yicheng Lu, Wenxiu Dong, Yinyi Zhou, Xiaolong Fu, Lulu Jiang, Chang Tan, Shanzhong Zhang, Sijie Sun, Huaien Song, Maoli Duan, Dingjun Zha, Yu Sun, Xia Gao, Lei Xu, Fan-Gang Zeng and Renjie Chai.
Journal: Nature Medicine
DOI: 10.1038/s41591-025-03773-w
Method of Research: Experimental study
Subject of Research: People
Article Title: AAV gene therapy for autosomal recessive deafness 9: a single-arm trial
Article Publication Date: 2-Jul-2025