A large international clinical trial has demonstrated that gene therapy can restore hearing in most patients with autosomal recessive deafness 9 (DFNB9), a rare inherited form of deafness caused by mutations in the OTOF gene. The study, co-led by researchers from Mass General Brigham and the Eye and ENT Hospital of Fudan University, is the largest clinical trial of gene therapy for inherited hearing loss to date and reports the longest follow-up period so far, with results sustained for up to 2.5 years. Findings are published in Nature.


DFNB9 results from mutations in the OTOF gene, which encodes otoferlin, a protein essential for transmitting auditory signals from inner-ear hair cells to the brain. Without functional otoferlin, individuals are born with severe to complete deafness. Genetic mutations account for up to 60% of congenital hearing loss, with OTOF mutations responsible for approximately 2 to 8% of cases.


The trial enrolled 42 participants aged between 0.8 and 32.3 years across eight sites in China. Each received a single injection into the inner ear delivering a functional copy of the OTOF gene via an adeno-associated virus (AAV) vector, at one of three doses. Thirty-six participants were treated in one ear and six in both ears.


Approximately 90% of participants showed hearing improvement in the treated ear, with gains observed within weeks of treatment and continuing over time. Speech recognition and language skills improved alongside auditory function. Younger patients and those treated in both ears demonstrated the greatest gains. Two of the three adult participants also showed measurable hearing recovery, a notable finding given that adults have largely been excluded from previous OTOF gene therapy trials. No serious treatment-related adverse effects were reported.


Researchers noted that around 10% of participants did not respond to therapy and plan to continue long-term follow-up, with a US trial under consideration.


Source: Jiang L et al. Multicentre gene therapy for OTOF-related deafness: follow-up to 2.5 years. Nature (2026). DOI: 10.1038/s41586-026-10393-y