Hearing restored by gene therapy in children with rare genetic deafness

A gene therapy trial in China has restored hearing in children born with a rare genetic form of deafness.

Researchers from Fudan University in Shanghai, China announced that four out of five children who received the treatment were now able to hear. Presenting their results at the 30th Annual Congress of the European Society for Gene and Cell Therapy in Brussels, Belgium, the researchers claimed that these patients were the first people ever to have their natural hearing pathway restored, a goal of several research groups including a clinical trial taking place in Cambridge (see BioNews 1212).

'Before the treatment, if you put [these children] in a movie theatre with the loudest sound, they wouldn't hear it,' Dr Zheng-Yi Chen, from Massachussets Eye and Ear Infirmary in Boston who helped design and plan the study told MIT Review. 'Now they can hear close to normal speech, and one can hear a whisper.'

The genetic condition is caused by a lack of the protein otoferlin, which transmit hearing signals from the inner ear's hair cells to the brain. A mutation in the OTOF gene, that encodes otoferlin, disrupts this communication and results in deafness.

The therapy involved injecting harmless viruses carrying DNA for a working copy of OTOF into part of the children's inner ears called the cochlea. The gene is too large to package inside a single virus, so has to be split into two sections that recombine inside the body, forming a complete gene able to guide the production of the missing otoferlin protein.

For the four children whose hearing improved: 'They reach maybe 60 to 65 percent of normal hearing,' according to Dr Yilai Shu, who presented the research.

The researchers suggest that the reason the treatment was ineffective in the fifth child could be because they already had immunity to the type of virus used to deliver the therapy, meaning their immune systems destroyed the therapy before it could deliver the new genetic material.

Otoferlin deficiency is very rare and causes only one to three percent of cases of inherited deafness. If successful in larger trials, gene therapy approaches may be adapted for other types of genetic hearing impairment.

'Any hearing improvement I would call a total win, and getting patients to moderate hearing loss is remarkable,' said Dr Lawrence Lustig, who studies treatments for hearing loss at Columbia University in New York, but was not involved in this research. 'This could be the gateway drug that drives a lot of funds toward other causes of deafness'.