Gene therapy trial restores hearing in both ears of children who were born deaf

A novel gene therapy designed to target a form of inherited deafness has restored hearing function in five children who were treated in both ears. The children also experienced better speech perception and gained the ability to localize and determine the position of sound.

The study, the world’s first clinical trial to administer gene therapy to both ears (bilaterally), demonstrates benefits in addition to those observed in the first phase of this trial, published earlier this year, when children were treated in one ear.

The research was led by investigators from Mass Eye and Ear and Eye & ENT Hospital of Fudan University in Shanghai, and the findings were published in Nature Medicine.

“The results from these studies are astounding,” said study co-senior author Zheng-Yi Chen, DPhil, an associate scientist in the Eaton-Peabody Laboratories at Mass Eye and 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, including the ability for sound source localization and improvements in speech recognition in noisy environments.”

The researchers noted their team’s goal was always to treat children in both ears to achieve the ability to hear sound in three dimensions, a capability important for communication and common daily tasks such as driving.

“Restoring hearing in both ears of children who are born deaf can maximize the benefits of hearing recovery,” said lead study author Yilai Shu MD, Ph.D., professor, director of Diagnosis and Treatment Center of Genetic Hearing Loss affiliated with the Eye & ENT Hospital of Fudan University in Shanghai, “These new results show this approach holds great promise and warrant larger international trials.”

Over 430 million people around the world are affected by disabling hearing loss, of which congenital deafness constitutes about 26 million of them. Up to 60% of childhood deafness is caused by genetic factors. Children with DFNB9 are born with mutations in the OTOF gene that prevent the production of functioning otoferlin protein, which is necessary for the auditory and neural mechanisms underlying hearing.

This new study is the first clinical trial to use bilateral ear gene therapy for treating DFNB9. The new research presents an interim analysis of a single-arm trial of five children with DFNB9 who were observed over either a 13-week or 26-week period at the Eye & ENT Hospital of Fudan University in Shanghai, China. Shu injected functioning copies of the human OTOF transgene carried by adeno-associated virus (AAV) into the inner ears of patients through a specialized, minimally invasive surgery.

The first case of bilateral treatment was conducted in July 2023. During follow-up, 36 adverse events were observed, but no dose-limiting toxicity or serious events occurred. All five children showed hearing recovery in both ears, with dramatic improvements in speech perception and sound localization. Two of the children gained an ability to appreciate music, a more complex auditory signal, and were observed dancing to music in videos captured for the study. The trial remains ongoing with participants continuing to be monitored.

In 2022, this research team delivered the first gene therapy in the world for DFNB9 as part of a trial of six patients in China treated in one ear. That trial, whose results were published in The Lancet in January 2024, showed that five of six children gained improvements in hearing and speech. Shu initially presented the data at the 30th Annual Congress of European Society of Gene and Cell Therapy (ESGCT) in Brussels, Belgium in October 2023, becoming the first in the world to report clinical data on using gene therapy to restore hearing.

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