A recent clinical study involving five children with inherited deafness has shown that gene therapy administered in both ears resulted in the restoration of hearing and speech. Other benefits observed included improved ability to locate the source of sound, better hearing in noisy environments, and for two of the children, the newfound ability to enjoy music. This pioneering trial represents the first attempt worldwide to use gene therapy to treat children with hereditary deafness in both ears. The researchers behind the study believe that their findings justify the need for larger international trials and suggest that this approach could also be helpful for other causes of deafness, both genetic and non-genetic.
A novel gene therapy designed to target.A type of inherited deafness was successfully treated, restoring hearing in five children who received treatment in both ears. The children also showed improved speech perception and gained the ability to locate and identify the source of sounds. This study, the first of its kind to test gene therapy in both ears, demonstrated more benefits than the initial phase of the trial, which only treated one ear. The research was conducted by experts from Mass Eye and Ear and the Eye & ENT Hospital of Fudan University.ty in Shanghai, and findings were published June 5th 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 toTreating children with hearing loss in both ears can help them develop the ability to hear in three dimensions, which is crucial for communication and everyday tasks like driving. According to Yilai Shu MD, PhD, lead author of the study, restoring hearing in both ears for deaf children can maximize the benefits of hearing recovery. The results of the study show great promise and call for larger international trials. Currently, over 430 million people worldwide are affected by disabling hearing loss.The number of people with hearing loss is around 466 million, with about 26 million of them having congenital deafness. Genetic factors account for up to 60% of childhood deafness. Children with DFNB9 have mutations in the OTOF gene, which prevents the production of otoferlin protein, essential for hearing mechanisms. This new study is the first to use bilateral ear gene therapy for treating DFNB9. The research presents an interim analysis of a single-arm trial of five children with DFNB9 observed over 13 or 26 weeks at the Eye & ENT Hospital of Fudan University.A university in Shanghai, China, Shu conducted a specialized, minimally invasive surgery to inject functioning copies of the human OTOF transgene carried by adeno-associated virus (AAV) into the inner ears of patients. The first case of bilateral treatment took place in July 2023. During the follow-up period, 36 adverse events were observed, but no dose-limiting toxicity or serious events occurred. All five children showed hearing improvement in both ears, with significant enhancements in speech perception and sound localization. Additionally, two of the children gained an appreciation for music and a greater ability to process complex auditory signals, and were even seen dancing to music.
The study included the use of music in the video recordings, and it is still ongoing with participants being monitored.
In 2022, the research team conducted the first gene therapy for DFNB9 in the world. This involved a trial of six patients in China, with treatment being administered in one ear. The results of this trial were published in The Lancet in January 2024, revealing that five out of six children experienced improvements in hearing and speech. The data was initially presented by Shu at the 30th annual congress of the European Society of Gene and Cell Therapy (ESGCT) in Brussels, Belgium in October 2023. This made Shu the first person in the world to report clinical data on the use of gene therapy.
Gene therapy has been used successfully in a clinical trial to restore hearing. Dr. Shu, who trained under Dr. Chen, stated that the results confirm the effectiveness of the treatment. The study supports the use of gene therapy in treating children with DFNB9 in both ears. The hope is that this approach can also be expanded to treat deafness caused by other genes or non-genetic causes.
“These results confirm the efficacy of the treatment that we previously reported on and represent a major step in gene therapy for genetic hearing loss,” said Shu. Shu trained under Chen for four years as a postdoctoral fellow at Mass Eye and Ear, with their collaboration continuing for more than a decade since he returned to Shanghai.
“Our study strongly supports treating children with DFNB9 in both ears, and our hope is this trial can expand and this approach can also be looked at for deafness caused by other genes or non-genetic causes,” added Chen, who is also an a
Associate professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School, Dr. Xun Chen, stated, “Our primary objective is to assist individuals in recovering their hearing regardless of the cause of their hearing loss.”
Currently, there are no medications accessible to treat genetic deafness, creating opportunities for innovative approaches like gene therapies.
The Gene and Cell Therapy Institute at Mass General Brigham is contributing to the advancement of scientific discoveries into initial human clinical trials. Dr. Chen and his team are collaborating with the Institute to create platforms and vectors that adhere to good manufacturing practice standards, allowing his team to work towards their goal.In order to easily test this therapeutic approach with other genes in the future, more work is needed to further study and refine the therapy. The bilateral study requires more consideration compared to the unilateral (one-ear) study as operations in both ears, in the course of one surgery, doubles the surgical time. Additionally, injecting double doses of AAVs into the body is likely to elicit a stronger immune response and increase the potential for adverse effects. Looking ahead, more patients and a longer follow-up duration are necessary, along with continued analysis of gene therapies and cochlear implants.Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.
Researchers found that gene therapy showed promising results in a small, single-arm trial for children with autosomal recessive deafness 9. The study, published in Nature Medicine, demonstrated improvements in hearing after treatment. The next step is to conduct larger randomized trials to further evaluate the therapy’s effectiveness.
