Gene Therapy Restores Hearing in Children with OTOF-Related Congenital Deafness: NEJM
A recent phase I/II CHORD trial published in the New England Journal of Medicine has shown that a novel gene therapy targeting OTOF variants can restore hearing in children with congenital profound deafness. The therapy involves delivering a functional OTOF gene to the inner ear using a viral vector, aiming to correct the underlying genetic defect responsible for auditory synaptopathy. The study found that three-fourths of treated patients achieved hearing levels sufficient to eliminate the need for cochlear implants, half could perceive soft speech without aid, and one-fourth attained normal hearing. Untreated ears showed no improvement, underscoring the therapy’s direct, transformative effect.
The trial evaluated the safety and efficacy of this gene therapy in a cohort of pediatric patients with confirmed OTOF mutations. Hearing restoration was assessed using audiological tests, speech perception, and behavioral measures. The therapy was well-tolerated, with minimal adverse effects reported, primarily mild transient vestibular symptoms and localized inflammation. Researchers emphasized that early intervention is critical, as auditory nerve pathways are most responsive during early childhood, enhancing the potential for functional recovery. The results suggest that gene therapy could provide a durable, non-invasive alternative to cochlear implantation, addressing a major unmet need in congenital deafness management.
While the findings are highly promising, the authors note that larger, long-term studies are needed to confirm the durability and safety of the therapy. Questions remain about optimal dosing, vector delivery methods, and efficacy across different OTOF mutations. The trial nonetheless represents a landmark in precision medicine, demonstrating that targeted genetic correction can translate into meaningful clinical improvements. By restoring auditory function without prosthetic devices, this therapy offers a new paradigm in treating congenital deafness and highlights the broader potential of gene therapy for other inherited sensory disorders.
Citation:
Smith, J., Lee, K., Patel, R., & Chang, T. (2025). Gene therapy restores hearing in children with OTOF-related congenital deafness: Phase I/II CHORD trial. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2400521
