Successful auditory therapy –

Five children with hereditary deafness have regained speech and hearing in both ears thanks to a gene therapy that has proven effective. After the trial, the children were able to locate and determine the position of sounds, reports EFE.

The clinical trial, conducted by researchers at Mass Eye and Ear and the Eye & ENT Hospital at Fudan University in Shanghai, China, demonstrated that hearing in both ears can be restored to five children with Dfnb9, an autosomal deafness caused by mutations in the Otof gene.

This is the first time that gene therapy has been successfully administered to both ears (bilaterally), as in the first phase of the study, published earlier this year, children were treated in only one ear.

The results of the trial were published in the journal “Nature Medicine.”

“The results of these studies are astonishing,” said Zheng-Yi Chen, co-senior author of the study and an associate scientist at Eaton-Peabody Laboratories at Mass Eye and Ear.

“The hearing ability of treated children continues to progress dramatically and the new study shows added benefits of gene therapy when administered to both ears, including the ability to localize sound sources and improvements in speech recognition in noisy environments,” he added.

The team’s goal was always to treat children in both ears to achieve the ability to hear sound in three dimensions, an important skill for communication and common everyday tasks like driving.

For that reason, “these new results show that this approach is very promising and warrants larger international trials,” said senior author Yilai Shu MD, of Fudan University Eye & ENT Hospital in Shanghai.

More than 430 million people worldwide suffer from disabling hearing loss, and of these, 26 million suffer from congenital deafness.

In children, up to 60% of cases are caused by genetic factors. Children with Dfnb9 are born with mutations in the Otof gene that prevent the production of the functional otoferlin protein, which is necessary for the auditory and neural mechanisms underlying hearing.

This new study—the first to use bilateral gene therapy in the ear—was conducted on five children with Dfnb9 over a period of 13 to 26 weeks at the Fudan University Eye and Ear Hospital.

Shu injected functional copies of the human Otof transgene carried by an adeno-associated virus (AAV) into the inner ears of patients using a specialized minimally invasive surgery. The first case of bilateral treatment was carried out in July 2023.

During follow-up, 36 adverse events were observed, but there were no dose-limiting toxicities or serious events.

All five children regained hearing in both ears, with dramatic improvements in speech perception and sound localization. Two of the children were also able to appreciate music, a more complex auditory signal.

The medical trial is ongoing and participants continue to be monitored.

First phase of the study

A year before carrying out this bilateral therapy, in 2022, this research team administered the world’s first gene therapy for DFNB9 with six patients who were treated in one ear.

That trial, the results of which were published in The Lancet in January 2024, showed that five of the six children improved their hearing and speech.

“These results confirm the efficacy of the treatment we previously reported and represent an important step in gene therapy for genetic hearing loss,” Shu said following carrying out the bilateral therapy.

The team’s ultimate goal is to help people regain their hearing regardless of the cause of their hearing loss.

Currently, there are no drugs to treat inherited deafness, which has given way to novel interventions such as gene therapies.

The authors note that further study and refinement of the therapy is necessary.