A gene therapy has successfully restored hearing in five children with inherited deafness
This world-first trial, targeting both ears, was led by researchers from Mass Eye and Ear in collaboration with Eye & ENT Hospital of Fudan University in Shanghai. The results were published on June 5th in Nature Medicine.
Children born with genetic mutation
The children, born with a genetic mutation known as DFNB9, lack the otoferlin protein essential for hearing. By delivering functional copies of the OTOF gene via adeno-associated virus (AAV) into their inner ears, the researchers observed remarkable improvements in hearing, speech perception, and sound localisation.
“Restoring hearing in both ears of children who are born deaf can maximize the benefits of hearing recovery,” explained Dr. Yilai Shu, the lead study author. Shu, a professor at Fudan University, highlighted the enhanced ability to locate and interpret sounds in three dimensions, a critical skill for daily activities like driving.
The trial marks a significant advancement from an earlier phase, where children were treated in only one ear. “We continue to see the hearing ability of treated children dramatically progress and the new study shows added benefits of the gene therapy when administrated to both ears,” said co-senior author Zheng-Yi Chen, DPhil, from Mass Eye and Ear. Chen emphasised the additional benefits of bilateral treatment, including better speech recognition in noisy environments.
Improvement in hearing for children with DFNB9
This research represents an interim analysis of a single-arm trial where five children with DFNB9 were monitored for 13 to 26 weeks. The first bilateral treatment was conducted in July 2023, and despite observing 36 adverse events, none were serious or dose-limiting. All five children showed significant improvements, with two even developing an appreciation for music.
In 2022, the team conducted the first-ever gene therapy trial for DFNB9, treating six children in one ear. The results, published in The Lancet in January 2024, showed five of six children experiencing improved hearing and speech. This earlier success set the stage for the current bilateral trial.
Shu and Chen have been collaborating for over a decade, striving to expand this therapy’s applications. “Our study strongly supports treating children with DFNB9 in both ears,” said Chen, also an associate professor at Harvard Medical School.
430 million people globally affected by disabling hearing loss
Treating both ears doubles the surgical time and potential for immune responses, making further study crucial. The Gene and Cell Therapy Institute at Mass General Brigham is supporting the development of scalable gene therapy platforms to facilitate future trials.
With over 430 million people globally affected by disabling hearing loss, including 26 million with congenital deafness, this therapy offers hope for a future where genetic hearing loss can be effectively treated.
