A groundbreaking genetic therapy developed by Chinese medical experts shows great promise in curing hereditary deafness during clinical trials, bringing new hope to millions of people with congenital hearing loss.

The research, published on Jan 25 in the esteemed medical journal The Lancet, states that the therapy has proven safe and effective as a novel treatment for children with autosomal recessive deafness 9.

Led by researchers from the Eye and ENT Hospital of Fudan University in Shanghai, in collaboration with Harvard Medical School, Southwest University and the Shanghai Refreshgene Therapeutics Co, the team used a method in which normally functioning human-source genes were "transported" to the inner ear cells of patients, replacing the dysfunctional genes with functional ones.

Specifically targeting OTOF, a protein-coding gene associated with deafness due to mutations, the team used an adeno-associated virus, a commonly used "cargo truck" in genetic therapy, to deliver the genes into target cells in the cochlea.

The idea may seem straightforward, but the actual process was much more challenging. A key obstacle was that the size of the functional gene sequence, or the "cargo," was larger than the AAV, or the "truck."

"We used two 'trucks' to each deliver a part of the gene sequence and then reassembled them inside the target cells," said Shu Yilai, the project leader and a corresponding author of The Lancet paper. "The key to the therapy lies in how to deconstruct the sequence and still make it functional after reassembling the parts."

Approximately 26 million people worldwide have hereditary deafness, and about 30,000 children in China are born deaf, with 60 percent of the cases related to genetic factors, according to the team.

The clinical trial began in October 2022 after receiving ethical approval in June 2022, and six people had enrolled as of June last year. The participants received the therapy through minimally invasive ear injections.

After six months of treatment, known as AAV1-hOTOF, five children experienced hearing recovery, responding to sounds from around 40 to 57 decibels, approximately the normal loudness of an indoor conversation. This improvement was observed in their speech perception as well.

Before the treatment, their sound response threshold was above 95 decibels. Importantly, no dose-limiting toxicity or serious adverse events occurred, proving the safety of the novel therapy in addition to its efficacy.

Researchers believe that this is the world's first effective clinical trial of genetic therapy to treat hereditary hearing loss, as well as the most systematic one, with the highest number of patients and the longest post-treatment follow-up observation periods.

"We fully support and actively encourage cutting-edge exploration in science and clinical translational research, strive to overcome challenges, and look forward to more epoch-making breakthroughs to better safeguard public health," said Zhou Xingtao, director of the Eye and ENT Hospital of Fudan University.