A multicenter study found a one-time treatment targeting the OTOF gene restored hearing in most participants, with effects lasting up to 2.5 years.
An international study co-led by investigators from Mass General Brigham and the Eye & ENT Hospital of Fudan University shows that a gene therapy for a rare form of genetic deafness restored hearing in approximately 90% of participants, with results lasting up to 2.5 years. The findings from the clinical trial, which had the longest follow-up reported to date for this type of therapy, were published in Nature.
The study focused on autosomal recessive deafness 9 (DFNB9), a condition caused by mutations in the OTOF gene. This gene provides instructions for making otoferlin, a protein essential for inner ear hair cells to transmit sound signals to the brain. Mutations in the OTOF gene account for about 2% to 8% of congenital hearing loss cases.
“It’s remarkable to see patients go from complete deafness to being able to hear,” says the study’s corresponding author, Zheng-Yi Chen, DPhil, an associate scientist at Mass Eye and Ear, a member of the Mass General Brigham healthcare system. “For many patients, that also means the ability to develop and use speech.”
“These results show that restoring hearing is possible even after years of deafness. We are now working to expand this approach to other genetic causes of hearing loss.” — Yilai Shu, MD, PhD
Trial Methodology and Treatment
The treatment consists of a single injection into the inner ear using a harmless adeno-associated virus (AAV) to deliver a working copy of the OTOF gene to the necessary cells. The trial enrolled 42 participants, ranging from infants to adults (0.8 to 32.3 years old), across eight sites in China. Of the participants, 36 received the treatment in one ear and six received it in both ears. The research team followed the participants for up to 2.5 years to monitor safety, hearing restoration, and speech recognition.
“These multicenter trial results validate the effectiveness of our OTOF gene therapy,” says Yilai Shu, MD, PhD, a professor from Eye & ENT Hospital of Fudan University, who led the study. “The procedure can be broadly implemented in hospital settings, ensuring consistent delivery for a larger patient population.”
Key Findings and Clinical Implications
The study reported no serious treatment-related side effects. Key findings include:
- Approximately 90% of participants experienced hearing improvement in the treated ear, with most showing improvement within weeks that continued over time.
- As hearing returned, participants demonstrated improved speech understanding and language skills.
- Younger children and those with healthier inner ears showed the greatest improvements.
- Participants treated in both ears had higher language and speech scores compared to those treated in one ear.
- Two of the three adult participants showed hearing recovery, though at smaller levels compared to younger participants.
“It is very encouraging to see meaningful improvements in some adult patients,” says Chen. “It suggests there may be more flexibility in the human auditory system than we expected.”
Researchers noted that about 10% of participants did not respond to the therapy. The team plans to continue long-term follow-up with the participants and hopes to begin a trial in the US. They are also exploring gene therapies for other forms of genetic hearing loss.
“These results show that restoring hearing is possible even after years of deafness,” says Shu. “We are now working to expand this approach to other genetic causes of hearing loss.”
Featured image: Dreamstime
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