Gene therapy enables five children who were born deaf to hear

Five children in China who were born deaf can now hear with both ears after getting gene therapy to provide a normal copy of a mutated gene. The degree of hearing varies from child to child, but all can now hear voices at a conversational volume and locate the source of sounds.

Six months after treatment, the five children’s hearing was around 50 to 60 per cent of normal levels, says team member Zheng-Yi Chen at the Mass Eye and Ear hospital in Boston. “When we whisper, they have a difficult time, but normal conversation is fine,” he says. “We’re very happy.”

In the first part of this trial, which began in 2022, the team gave a separate group of six children in China gene therapy in one ear only. Five of the six gained hearing in the treated ear and are still continuously improving, says Chen.

The team expects the second group of five children to see further gains too. “What we see now is not the peak of the improvement,” says Chen. “We expect it to improve further.”

The trial in China is the first of several getting under way around the world, with two children in the UK and one in the US also reported to have gained hearing in one ear after receiving gene therapy.

“The trials are all broadly similar,” says Manohar Bance at the University of Cambridge, who treated the two children in the UK.

All the children in these trials were born deaf because they have mutations in both copies of the gene for a protein called otoferlin. This plays a key role in the synapses, or links, between the hair cells in the ear that detect sound and the nerves that carry the signals to the brain. The mutations affect the protein, stopping the signals from being transmitted.

Between 2 and 8 per cent of the children born deaf around the world are thought to have this condition, known as DFNB9.

The parents of children with DFNB9 have normal hearing if they each have just one mutated copy of otoferlin. Such couples are usually unaware they have a 1 in 4 chance of having a child who is born deaf.

The gene therapy involves delivering a working version of the otoferlin gene to the hair cells with the help of a virus called AAV. Because of the size of the otoferlin gene, it has to be split and put into two separate viruses.

A mixture of the viruses is injected into the inner ear and the complete gene is then reassembled inside cells that get both of its halves. The DFNB9 trials are the first time that dual AAV gene therapy, as it is known, has been used to treat people.

“This is a big technological advancement,” says Chen. “We expect to see very broad use of the technology for treating other genetic diseases.”

The trials start by treating just one ear at a time because this requires half the dose of AAV, he says, reducing the odds of any adverse events. No serious adverse events have been reported in any of the trials.

Chen’s team now plans to treat the other ear of the children in the first group. This might be tricky because the immune response to the initial AAV injection could block gene delivery, but Chen thinks it will be possible.

Treating other forms of inherited deafness will be harder, says Chen, because these result in the degeneration of some structures within the ear. With DFNB9, all the structures remain intact. “We just need to fix one component,” he says.

Some people don’t see deafness as a condition that needs to be cured, says Martin McLean at the UK’s National Deaf Children’s Society. The society’s position is that families should be free to make informed decisions for themselves.

“Parents or young people should be made aware of any risks, and above all understand that being deaf is not a barrier in itself to a happy and fulfilled life,” he says.