A recent international study from researchers at Mass General Brigham and the Eye & ENT Hospital of Fudan University demonstrates the potential of gene therapy to restore hearing in patients with a rare form of genetic deafness. The groundbreaking findings, reported in Nature, reveal that the therapy successfully improved hearing for most participants, with results lasting up to 2.5 years. This study represents the largest clinical trial on gene therapy for hereditary hearing loss to date, as well as the longest follow-up period reported.
“It is remarkable to witness patients transition from complete deafness to usable hearing abilities,” said Zheng-Yi Chen, DPhil, the study’s corresponding author and an associate scientist at Mass Eye and Ear. “For many participants, this also means the ability to develop and utilize language.”
Genetic mutations account for approximately 60% of congenital hearing loss cases. This research focused on gene therapy specifically designed for autosomal recessive deafness type 9 (DFNB9), caused by mutations in the OTOF gene. The OTOF gene provides instructions for producing Otoferlin, a protein essential for hearing. In its absence, sensory hair cells in the inner ear are unable to transmit sound signals to the brain, leading to profound deafness at birth. OTOF mutations contribute to about 2 to 8 out of every 100 congenital hearing loss cases.
Gene therapies aim to introduce a functional version of mutated genes that are responsible for certain diseases. Given that a single faulty gene causes DFNB9, it makes it an ideal target for gene therapy research. The treatment involves a single injection into the inner ear, using a harmless virus (AAV) to deliver a working copy of the OTOF gene into the necessary auditory cells.
The study involved 42 participants ranging from infants to adults (ages 0.8 to 32.3 years) across eight sites in China. Each participant received one of three doses of the gene therapy: 36 received treatment in one ear, and six were treated in both ears. Participants were monitored for up to 2.5 years to assess the safety of the treatment as well as its impact on their hearing and speech recognition abilities. The researchers also sought to understand variances in treatment responses among participants.
“The results from this multicenter trial confirm the efficacy of our OTOF gene therapy,” stated Dr. Yilai Shu, professor at the Eye & ENT Hospital of Fudan University and the lead investigator. “The procedure can be comprehensively implemented within hospital settings, ensuring consistent care for a broader patient population.”
No severe treatment-related side effects were reported among participants. Approximately 90% of those treated noted improvements in hearing in the affected ear, with many experiencing enhancements just weeks post-treatment; these benefits continued over time. Restoration of hearing also enabled participants to better comprehend and develop speech. Notably, younger children and those with healthier inner ears demonstrated the most significant gains, while participants treated in both ears achieved higher speech and recognition scores compared to those treated in one ear. Among the three treated adults, two saw some recovery of hearing, albeit to a lesser degree than younger individuals.
It is very encouraging to observe notable improvements in some adult patients. “This suggests that the human auditory system may be more adaptable than we previously thought,” said Zheng-Yi Chen, DPhil.
This research complements previous positive findings by the same group involving five children who received gene therapy in both ears and six in one ear, all showing safety and improvement in hearing and speech, with findings anticipated for publication in 2024.
While data indicated that around 10% of participants did not respond to the therapy, the researchers plan to continue long-term monitoring and hope to initiate trials in the United States in the future. They are also exploring gene therapies for other forms of genetic hearing loss, developing a platform for addressing genetic mutations associated with hearing restoration.
“These outcomes indicate that restoring hearing is achievable even after years of deafness,” remarked Dr. Shu. “We are now focused on expanding this approach to other genetic causes of hearing loss.”
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Journal Reference:
Jiang, L., et al. (2026). A multicenter gene therapy for OTOF-related deafness followed for up to 2.5 years. Nature. DOI: 10.1038/s41586-026-10393-y. https://www.nature.com/articles/s41586-026-10393-y
