A trial of a gene therapy to treat people with hearing loss related to recessive mutations in the OTOF gene shows the treatment is effective and safe for at least 2.5 years.
The study, published in Nature, showed around 90% of those who received the adeno-associated viral (AAV) vector gene therapy showed at least some restoration in hearing.
Improvement was rapid in the first six weeks, improved further by 26 weeks and in a small subset of patients remained stable for 2.5 years of follow-up.
“It’s remarkable to see patients go from complete deafness to being able to hear,” said the study’s co-lead author, Zheng-Yi Chen, PhD, the Ines and Fredrick Yeatts Chair in Otolaryngology and an associate scientist at Massachusetts Eye and Ear hospital, in a press statement. “For many patients, that also means the ability to develop and use speech.”
The OTOF gene encodes the otoferlin protein, which is critical for normal hearing. When otoferlin is missing or nonfunctional, inner‑ear hair cells can’t relay sound information to the brain, leading to severe or complete deafness. This kind of hearing loss is rare and inherited in a recessive manner, needing mutations from both parents for a child to be affected.
As of this year there are at least five gene therapies being developed to treat this kind of deafness, for example, by Akouos/Eli Lilly and Decibel/Regeneron in the U.S., Sensorion in France, and at least two additional programs in China.
The current study took place in China and included 42 people between the age of eight months and 32 years (average age six years) and is the largest cohort of OTOF gene‑therapy patients reported so far, as well as the longest study follow-up period.
The participants received one of three doses of the AAV gene therapy injected into their cochlea’s and were followed up for 13 weeks to 2.5 years (median 52 weeks) to assess the impact of the therapy on hearing and also to evaluate safety.
Overall no serious adverse events or dose-limiting toxicities occurred. Around 90% of participants experienced hearing restoration to some degree with fast improvements seen in the first six weeks after treatment and slower improvements after that. A subset of patients (seven ears from seven patients) were included in the 2.5 year follow-up group and results were similar to those seen at two years.
Some groups did better than others. For example, hearing restoration was 100% in children aged up to three years and 92% in those aged 3-8 years. Improvement was seen in older children and adults, but to a lesser degree than that seen in young children in the study. Participants with better outer hair cell function on enrollment also responded better to the therapy than those with greater functional loss.
“It is very encouraging to see meaningful improvements in some adult patients. It suggests there may be more flexibility in the human auditory system than we expected,” said Chen, who is also the scientific founder of Salubritas Therapeutics, a Massachusetts based biotech focusing on hearing loss correction.
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