A novel gene therapy targeting inherited deafness has restored hearing function in five children treated in both ears, improving their speech perception and ability to localize sound. This breakthrough, marking the first clinical trial to administer gene therapy bilaterally, has shown enhanced benefits compared to earlier trials treating only one ear. The research, led by teams from Mass Eye and Ear (part of Mass General Brigham) and the Eye & ENT Hospital of Fudan University in Shanghai, was published in Nature Medicine on June 5th.
“The results from these studies are astounding,” said co-senior author Zheng-Yi Chen, DPhil, of Mass Eye and Ear. “We continue to see the hearing ability of treated children dramatically progress, with added benefits when gene therapy is administered to both ears, such as sound source localization and speech recognition improvements in noisy environments.”
The primary aim was to treat both ears to enable three-dimensional hearing, crucial for daily tasks and communication. “Restoring hearing in both ears can maximize recovery benefits,” stated lead author Yilai Shu, MD, PhD, from the Eye & ENT Hospital of Fudan University. “These new results show great promise and justify larger international trials.”
Globally, over 430 million people suffer from disabling hearing loss, with congenital deafness affecting about 26 million. Genetic factors cause up to 60 percent of childhood deafness, including DFNB9, which involves mutations in the OTOF gene, preventing the production of the otoferlin protein needed for hearing.
This study is the first to use bilateral gene therapy for DFNB9, involving a single-arm trial of five children observed over 13 or 26 weeks at Fudan University. Shu administered functioning copies of the human OTOF gene via adeno-associated virus (AAV) into the patients’ inner ears through minimally invasive surgery. The first bilateral treatment occurred in July 2023. Although 36 adverse events were noted, none were serious or dose-limiting. All five children experienced hearing recovery in both ears, with significant improvements in speech perception and sound localization. Two children even began to appreciate music, evidenced by their dancing in videos.
In 2022, the team conducted the first DFNB9 gene therapy trial on six children, treating one ear each, with published results in The Lancet in January 2024. Five children showed improved hearing and speech. Shu presented the data at the 30th annual ESGCT congress in Brussels, making it the first clinical report of gene therapy restoring hearing.
Chen, an associate professor at Harvard Medical School, emphasized the study’s support for bilateral treatment and its potential application to other genetic or non-genetic causes of deafness. Currently, no drugs exist for hereditary deafness, paving the way for innovative therapies like gene therapy. Mass General Brigham’s Gene and Cell Therapy Institute aids in translating research discoveries into clinical trials, facilitating future testing of various gene therapies.
Further studies are needed to refine the therapy, considering the increased surgical time and potential immune responses when treating both ears. Larger, randomized trials with longer follow-up periods are essential to evaluate the therapy’s efficacy and safety comprehensively.
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