Research has shown that an experimental gene therapy for inherited deafness has led to significant, lasting improvements in hearing and speech recognition. The therapy addresses mutations in the OTOF gene, one of approximately 200 genes linked to congenital deafness. The most notable improvements were observed in patients under 18, but adults also experienced benefits, albeit to a lesser extent. By the end of the 2½-year study, 90 percent of participants had better hearing, with half achieving normal hearing levels.
“How well it worked is really amazing,” stated Zheng-Yi Chen, a co-senior author of the study and associate professor at Harvard Medical School. The therapy has enabled more than half of the participants to hear whispers, a level of hearing that Chen himself does not possess. According to the World Health Organization, hearing loss affects about 430 million people globally, including 34 million children. Genetic factors account for 60 percent of newborn deafness cases, with the OTOF mutation causing 2 to 8 percent of these instances.
The research team is adapting the therapy platform to target other genetic causes of deafness, such as the GJB2 gene mutation, which is the most common genetic cause of hearing loss. The study, published in Nature, was conducted by institutions including Mass Eye and Ear, Harvard Medical School, and Fudan University, with trial sites in China. Initial trials in 2024 showed rapid hearing improvements in children, surprising researchers and parents.
The treatment focuses on DFNB9, a condition caused by the OTOF mutation, which disrupts the function of otoferlin in the cochlea. Researchers injected a harmless virus with a normal OTOF gene into patients’ inner ear fluid, allowing it to be expressed in cochlear hair cells and restoring hearing function. The study included 42 participants aged from nine months to 32 years, treated at eight centers in China. Some participants reported hearing improvements within two weeks, with significant gains plateauing around 26 weeks and persisting for 2½ years.
Chen highlighted the importance of the long-lasting effects, as early mouse experiments showed a decrease over time. The treatment was deemed safe, with no serious adverse effects or dose-related toxicity. Supported by Chinese and Shanghai governments and Fudan University, the research team is exploring regulatory approval in China, with hopes for international expansion. “The success of OTOF gene therapy marks a paradigm shift in treating hearing loss,” said Yilai Shu, co-senior author of the study.
Chen noted that ongoing research will follow participants for five years to address why some did not respond to treatment and why adults showed less improvement than younger patients. He expressed optimism about future trials and advancements for patients. “We’re looking forward to what the future will bring for patients,” added Chen.
Original Source: news.harvard.edu
