To get the new genetic material into cells, they engineered a harmless virus that carries it. Doctors carefully injected tiny amounts of the virus-containing fluid into an area of the children’s inner ears called the cochlea, a spiral-shaped chamber that contains hair cells. The first patient in the trial received gene therapy in December 2022. The researchers followed the participants, who were between 1 and 6 years old, for 23 weeks after treatment.
Although the gene therapy did not bring the children’s hearing to a “normal” level, they went from not being able to hear sounds below 95 decibels (about the same volume as a food processor or a motorcycle) to typical hearing levels. They can now perceive sounds of approximately 45 decibels. Conversations and refrigerator noises.
“The family is very, very excited,” said Eli Xu, a head and neck surgeon at Fudan University Eye and Ear, Nose and Throat Hospital and author of the paper. For some parents, this is the first time they hear their child say “mama” or “baba” (meaning “daddy” in Chinese).
The other children in the study had previously received a cochlear implant in one ear and were already learning to speak. In such cases, doctors injected a gene therapy drug into the other ear. A cochlear implant is a surgically implanted device that stimulates the auditory nerve to provide the wearer with the sensation of sound. However, implants do not replicate natural hearing. The resulting sound can be robotic or distorted. And when the switch is turned off, the wearer can’t hear at all.
Researchers aim to provide natural hearing through gene therapy. A follow-up study of the patients after the injections included turning off the cochlear implants and assessing how well the treatment was working for the children.
“They became more engaged and responsive. It’s like a personality change,” said Zheng-Yi Chen, an associate scientist at Mass Eye and Ear who co-led the study. Masu.
One child’s hearing did not improve at all. One explanation, Professor Hsu said, is that the child already had immunity to the type of virus used to deliver new genes to inner ear cells. This means that the immune system destroys the treatment before it can be effective. It’s also possible that the dose was too low to be effective, Lustig said.
Several companies are advancing gene therapy for this same cause of hearing loss. Boston-based Aquos, which was acquired by Eli Lilly in 2022, has treated two people in clinical trials that began last year.Eli Lilly announced this week One of the participants, an 11-year-old boy, was able to hear within 30 days of receiving otoferlin gene therapy.
And in October, Regeneron’s Decibel Therapeutics was held in Boston. An improvement in auditory response was reported in one patient. As part of an ongoing clinical trial. China’s Otovia Therapeutics and France’s Sensorion are also working on similar treatments. The Fudan University trial reported today was funded by Refresh Gene Therapeutics of Shanghai.
Colin Johnson, a biochemist at Oregon State University who studies otoferlin, called the results of the Chinese and U.S. studies “a dramatic development.” Scientists have been interested in restoring otoferlin for years, but have struggled with ways to incorporate the gene into virus particles. The otoferlin gene is large, approximately 6,000 DNA letters long, and is not compatible with viruses used in gene therapy. Scientists eventually discovered that they could split the gene into two parts and deliver each part separately. When tested in mice, the gene combined in the inner ear, allowing the mice to hear.