This revolutionary feat in medical research is the result of the world’s first clinical trial that involved giving gene therapy to both ears in children who were born deaf due to inheritance. There are currently no pharmaceutical treatments for congenital deafness, a disorder that affects over 26 million people globally.
Gene therapy has gained popularity recently as a potentially effective therapeutic option for millions of people to enhance their quality of life and restore their hearing. Children with OTOF gene mutations that result in autosomal deafness were the subject of the clinical trial, which was conducted at the Eye & ENT Hospital of Fudan University in Shanghai in association with researchers from the Mass Eye and Ear Hospital in Boston, Massachusetts.
“The results from these studies are astounding,” said Zheng-Yi Chen, study co-senior author and 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 administered to both ears, including the ability for sound source localization and improvements in speech recognition in noisy environments,” Chen added.
Genetic factors account for up to 60% of childhood deafness. Mutations in the OTOF gene cause autosomal recessive deafness 9 (DFNB9), which impedes the formation of otoferlin, a protein required to transmit sound impulses from the ear’s cochlea to the brain.
This trial builds on a previous phase where treatment was provided to one ear. However, restoring hearing in both ears is crucial for perceiving sounds in three dimensions, essential for effective communication and everyday tasks like driving.
In this bilateral trial, gene therapy was delivered to both ears of five children, starting with the first child in July 2023. The therapy involved delivering functional copies of the OTOF gene via adeno-associated virus (AAV) into the inner ear. AAV is a modified virus that ferries genes into target cells with minimal pathogenicity, making it suitable for gene therapy.
A specialized, minimally invasive surgery was performed to deliver the gene therapy, and the children were monitored for 13 or 26 weeks. Although 36 adverse events were reported, none were serious or dose-limiting. The results showed that all five children experienced hearing recovery in both ears, with improvements in speech understanding and sound localization. Two children even developed an appreciation for music, indicating the therapy’s potential to restore complex auditory functions.
“Our study strongly supports treating children with DFNB9 in both ears, and our hope is this trial can expand and be applied to other causes of deafness,” said Chen. If approved, this gene therapy could restore hearing to millions of children worldwide.