A breakthrough clinical trial using gene therapy has restored hearing to five children born deaf. After six months, the children were able to recognize speech and hold conversations, raising hopes for wider use in the near future.
The patients in the trial suffered from a genetic condition called autosomal recessive deafness 9 (DFNB9), which is caused by a mutation in a gene called OTOF. This gene produces the otoferlin protein, which helps transmit electrical pulses from the cochlea to the brain, where it can be interpreted as sound – but without it, those signals never get there. Because it’s caused by a single mutation, and doesn’t involve any physical damage to cells, the team says DFNB9 was the perfect candidate for this kind of gene therapy.
The gene therapy involves packaging the OTOF gene into viral carriers, and injecting the mix into the inner ear fluid. The viruses then sought out cells in the cochlea and inserted the gene into them, which allows them to start manufacturing the missing otoferlin protein and restore hearing.
The study was conducted in China by researchers at Harvard Medical School, Massachusetts Eye and Ear, and Fudan University. The six participants were all children aged between one and seven years old, with DFNB9 rendering them completely deaf. Four patients had cochlear implants fitted, which bypasses the problem and can allow them to learn to recognize speech and other sound. In this case, the implants were switched off.
After the gene therapy, the children were followed up for 26 weeks. In that time, five out of six showed significant improvements – the three older children could understand and respond to speech, while two could pick it out in a noisy room and hold a conversation on the phone. Some of the kids were too young for the usual tests, but were found to respond to sounds and even began to verbalize simple words like “mama.” The improvements were gradual, but the team reports that the kids started showing results before their first test at the four-week mark.
“We first found out when the parents told us: When her mother called her, she turned back,” said Yilai Shu, senior author of the study. “All of them are very hopeful. They were very, very excited, and all of them cried when they first found that their child can hear.”
The sixth participant, unfortunately, didn’t respond to the treatment. While the researchers aren’t yet sure why, they suspect the viral vector was disrupted by an immune reaction. Further study could help find a way around this hurdle.
The researchers say that the participants in this trial will continue to be monitored, while follow-up studies will be conducted on other people. Approval of the treatment in the US could be three to five years away, the team says. Similar gene therapies have been tested for hearing loss with genetic or age-related causes.
The research was published in the journal Science Advances. The results can be seen in action in the video below.
Source: Harvard
