Gene therapy improves hearing in deaf patients within weeks

A gene therapy for inherited deafness has safely and rapidly improved hearing in patients ranging from early childhood to adulthood.

In collaboration with hospitals and universities in China, researchers at Karolinska Institutet in Stockholm, Sweden, have conducted a clinical trial of an adeno-associated virus (AAV) gene therapy for an autosomal recessive form of deafness in patients aged one to 24 years. All patients showed significant hearing improvements within six months of treatment, with most hearing restored within the first month.

'Smaller studies in China have previously shown positive results in children, but this is the first time that the method has been tested in teenagers and adults, too,' Dr Maoli Duan from the Karolinska Institutet and joint corresponding author of the paper published in Nature Medicine said. 'Hearing was greatly improved in many of the participants, which can have a profound effect on their life quality.'

The clinical trial included ten participants, all of whom had a genetic form of deafness or severe hearing impairment caused by mutations in a gene called OTOF. These mutations cause a deficiency of the protein otoferlin, which plays a critical role in transmitting sound signals from the inner ear to the brain. In the trial, the gene therapy used a vector – a synthetic version of the AAV – to deliver a functional version of the OTOF gene to the inner ear via a single injection.

Dr Duan additionally noted that 'this is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults.'

While various gene therapies across Europe, China and the USA have already demonstrated hearing restoration in children (see BioNews 1279, 1242 and 1212), this study marks the first clinical trial to include and improve hearing in an older adolescent and an adult.

The researchers reported that optimal outcomes were achieved in children aged five to eight years. In comparison, younger and older participants experienced less dramatic hearing improvement. Given the preservation of inner ear structure and function at younger ages, this observation was contrary to expectation for patients aged under five years old. While researchers proposed some possible explanations, the reasons for this remain unclear.

On average, the volume of perceptible sound across all participants improved from 106 decibels to 52 decibels within six to 12 months. One patient, aged seven, was able to have daily conversations with her mother just four months after treatment.

Follow-up in the six to 12 months following treatment revealed that the therapy was well-tolerated, with no serious adverse effects reported. Of the mild to moderate side effects observed, the most common was a decrease in white blood cell count.

'OTOF is just the beginning,' said Dr Duan. 'We and other researchers are expanding our work to other, more common genes that cause deafness, such as GJB2 and TMC1. These are more complicated to treat, but animal studies have so far returned promising results. We are confident that patients with different kinds of genetic deafness will one day be able to receive treatment.'