(CN) — Five children born deaf can now hear in both ears after a trial of a novel gene therapy focused on repairing a hereditary dysfunction that prevents auditory signals from reaching the brain, according to authors of a study published in the journal Nature Medicine Wednesday.
The success of the therapy in both ears demonstrates that the treatment can restore a full range of hearing functions including identifying the locations of sounds, recognizing specific sounds in noisy environments and the ability to perceive and develop speech.
The researchers used a minimally invasive surgical procedure to inject vector viruses into the inner ear. The viruses transfer genes into specialized cells that convert physical sound waves into the electrical signals that can be transmitted by nerve cells.
The new genetic material allows the cells to correctly replicate a protein that is necessary to send the converted electrical signals from the inner ear to the brain.
Family members noticed initial signs that their children could recognize sounds two weeks after application of the therapy. All the children were born deaf, four of them were between one and three years of age and the fifth participant was an 11-year-old.
At four to six weeks the children would turn to face the sound when a parent called to them from outside of their plane of view. At 13 to 15 weeks children could dance to music and form simple syllables, and at 26 weeks the children used complete words and showed more advanced communication.
“It’s very emotional for the whole family and even for my team, some of my students were so touched that they began to cry,” said lead study author Dr. Yilai Shu, director of the Diagnoses and Treatment Center of Genetic Hearing Loss affiliated with the Eye and ENT Hospital of Fudan University in Shanghai.
The successful trials grew out of a collaboration between Shu and the study’s co-senior author Zheng-Yi Chen, associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear in Boston. Shu was a student of Chen’s and they worked together during Shu’s postdoctoral fellowship at Mass Eye and Ear. Shu returned to China over a decade ago, but the two scientists continued to collaborate.
The research team conducted the trials at the Eye and ENT Hospital of Fudan in Shanghi, China.
The five children that participated have a specific genetic disorder caused by the mutation of a single gene that prevents the cells in the inner from replicating the protein otoferlin that is crucial for sound signal transmission via the nervous system.
Globally, 430 million people have some form of disabling hearing loss, according to the World Health Organization. About 26 million people were born with hearing loss and 60% of those cases are due to genetic factors, the study's authors say.
“This really opens a new era in treating hearing loss because there are over 150 genes that can cause genetic deafness,” Shu said.
In animal trials, the research team has shown that gene therapies are effective in treating several of these forms of genetic deafness, said Chen. The team’s successful treatment of the otoferlin genetic deficiency in humans means that the other models with proven success in animals can now move into human trials.
Eventually, the researchers hope to develop gene therapies for noise and age-related deafness as well.
One of the challenges of using the viral vector gene therapy with the otoferlin gene is that the gene itself is too large for the virus to carry, said Shu. To overcome this the researchers used a new technique that involves splitting the gene in half and allowing viruses to carry each half into the cells where the gene can recombine.
“This is actually a technology breakthrough,” said Chen, “So many genes for human diseases are also very big so this approach can be broadly applied in gene therapies to treat other diseases, not only deafness.”
In January the research team published the results of a trial conducted in 2022 which successfully tested the therapy in one ear. The bilateral trial involving two ears, which has allowed for participants to recover a full range of hearing functions including ability to detect the location of sound, requires a procedure for each ear resulting in an increased dosage of the viral vector.
The researchers choose to test the therapy in one ear first because the additional dosage of the viral vector is more likely to trigger an immune response which can lead to adverse affects. All five children involved in the bilateral study recovered their hearing and the adverse affects that researchers detected such as fever or elevated white blood count were well below the safety threshold.
Chen, who is also an associate professor of Otolaryngology–Head and Neck Surgery at Harvard Medical School said that international cooperation has been important to developing the treatment and Shu agrees.
“This type of research is very difficult and relies on decades of international study,” Shu said.
“We want to use this as an example that there is a future for this kind of collaboration,” Chen said. “It’s not a political issue it’s really just for human health and a common benefit for all of us.”
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