0
0
In a groundbreaking development, researchers from the Massachusetts Eye and Ear Infirmary have successfully conducted the first human clinical trial for a gene therapy designed to restore hearing function in children with hereditary deafness. The trial, conducted in December 2022 in China, targeted children with autosomal recessive deafness caused by mutations of the OTOF gene, known as DFNB9. The results, published in The Lancet, revealed the gene therapy’s remarkable effectiveness.
Hereditary deafness affects millions worldwide, and congenital deafness constitutes a significant portion of cases. DFNB9 is caused by mutations in the OTOF gene, resulting in the failure to produce a functional otoferlin protein crucial for transmitting sound signals from the ear to the brain. Currently, there are no FDA-approved drugs for hereditary deafness, making gene therapies a promising avenue for treatment.
During the trial, researchers used an adeno-associated virus (AAV) to deliver a version of the human OTOF gene into the inner ears of six children with DFNB9. The carefully administered gene therapy demonstrated safety and efficacy over a 26-week observation period at the Eye & ENT Hospital of Fudan University in China. The results showed significant hearing recovery in five children, with a notable reduction in auditory brainstem response (ABR) thresholds, improvements in speech perception, and the restoration of the ability to engage in normal conversation.
The researchers used varying doses of the single viral vector injection and reported no dose-limiting toxicity. During follow-up, 48 adverse events were observed, with the majority being low-grade (96 percent) and the rest being transitory with no long-term impact. The study not only supports the safety and effectiveness of gene therapies for treating DFNB9 but also highlights their potential for addressing other forms of genetic hearing loss.
Dr. Zheng-Yi Chen, Associate Scientist at Mass Eye and Ear, emphasized the remarkable results of the study, noting the significant improvement in the hearing ability of children over the 26-week period. The success of this gene therapy opens new possibilities for the treatment of hereditary deafness, offering hope to millions of individuals affected by genetic hearing conditions worldwide.
