A new international study jointly conducted by Massachusetts General Brigham researchers and Fudan University Eye and Ear, Nose and Throat Hospital shows that gene therapy for a rare form of inherited hearing loss was successful in restoring hearing in most participants, with effects lasting up to two and a half years. The results represent the largest clinical trial of gene therapy for inherited hearing loss to date and the longest follow-up ever reported. nature. The authors say these latest findings support previous trials showing that gene therapy can be used to treat some inherited forms of hearing loss, and will guide future research and treatment.
“It’s amazing to see patients go from complete hearing loss to hearing,” said the study’s corresponding author, Dr. Chen-Yi Chen, the Innes and Fredrick Yates Professor of Otolaryngology and an associate scientist at Mass Eye and Ear, a member of the Massachusetts General Brigham Healthcare System. “For many patients, it also means the ability to develop and use language.”
Genetic mutations account for up to 60% of hearing loss present at birth. In this study, researchers used a gene therapy they developed to treat autosomal recessive hearing loss type 9 (DFNB9), which is caused by a hearing-impairing mutation. Otoff gene. The OTOF gene instructs the body to produce a protein called otoferlin, which is essential for hearing function. Without this, the hair cells in the inner ear cannot transmit sound signals to the brain, causing severe to complete hearing loss at birth. OTOF mutations occur in approximately 2 to 8 out of 100 cases.
Gene therapy is designed to add a working version of a mutated gene that causes a disease. A single defective gene causes DFNB9, making it suitable for gene therapy studies. The treatment is a single injection into the inner ear using an harmless virus (AAV) to deliver a working copy of the OTOF gene to the cells needed for hearing.
This latest trial enrolled 42 participants ranging in age from infants to adults (0.8 to 32.3 years) at eight sites in China. Each participant received one of three doses of gene therapy, 36 in one ear and 6 in both ears. The researchers then followed the participants for up to two-and-a-half years to see if the treatment remained safe and had an effect on their hearing and speech recognition. The researchers also sought to better understand why some participants responded better than others.
“The results of these multicenter trials demonstrate the efficacy of our OTOF gene therapy,” said Yilai Shu, MD, professor at Fudan University Eye and Otorhinolaryngology Hospital, who led the study. “This procedure can be widely implemented in hospital settings to ensure consistent care for a larger patient population.”
They found no serious treatment-related side effects in trial participants. Approximately 90% of patients noticed improvement in their hearing in the treated ear, mostly within a few weeks after treatment, and the improvement continued over time. Once their hearing was restored, the participants were able to better understand speech and their language skills improved. Younger children and those with healthy inner ears saw the greatest improvements, with participants treated in both ears having higher language and speech scores than those treated in one ear. Of the three treated adults, two showed hearing recovery, but the level was smaller than in the younger participants. Adults have been largely excluded from OTOF gene therapy trials to date.
It is very encouraging to see meaningful improvement in some adult patients. This suggests that the human auditory system may be more flexible than we expected. ”
Zheng-Yi Chen, DPhil, Ines and Fredrick Yeatts Chair in Otolaryngology, Associate Scientist at Mass Eye and Ear
The paper adds to the group’s positive data found in a study published in 2024 of five children who received gene therapy in both ears and six children in one ear. Both studies established safety and showed that gene therapy can improve hearing and language.
Researchers note that about 10% of participants did not respond to treatment. The company plans to continue long-term follow-up and hopes to start clinical trials in the United States in the future. Researchers are also exploring gene therapies for other forms of inherited hearing loss, including developing platforms that can edit genetic mutations to restore hearing.
“These results show that it is possible to restore hearing even after years of hearing loss,” Shu said. “We are now working to extend this approach to other genetic causes of hearing loss.”
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Reference magazines:
Jean, L. Others. (2026). Multicenter gene therapy for OTOF-associated hearing loss was followed for up to 2.5 years. nature. DOI: 10.1038/s41586-026-10393-y. https://www.nature.com/articles/s41586-026-10393-y
