Deaf children can now hear after a single injection

The news follows an announcement that yet another child born with profound deafness can hear after receiving a similar treatment developed by US drugmaker Eli Lilly. The children were all born with a mutation in a gene that makes a protein needed for hearing called otoferlin. We hear things when sound waves in the air cause the thousands of sensory hair cells in our inner ears to vibrate and release a chemical that relays that information to the brain. Otoferlin is necessary for the release of this chemical messenger. Without it, the ear can’t communicate with the brain. More than half of hearing loss cases in children are due to genetic causes, and otoferlin mutations account for one to eight percent of those, affecting about 200,000 people worldwide. The treatment the children received works by delivering a working version of the otoferlin gene to the inner ear. The cells of the inner ear then read this gene and produce the protein. In the US and Europe, a handful of these cutting-edge therapies have been approved, including one for a type of inherited blindness. Given just once, they’re designed to correct disease-causing genes—hopefully permanently. For the deafness treatment, researchers at the Eye & ENT Hospital of Fudan University in Shanghai collaborated with a team at Mass Ear and Eye, a Harvard-affiliated hospital in Boston. To get the new genetic material into cells, they engineered harmless viruses to carry it. Doctors carefully injected a tiny amount of liquid containing the viruses into a part of the children’s inner ears called the cochlea, a spiral-shaped chamber that contains hair cells. The first patient in the trial received the gene therapy in December 2022. Researchers followed the participants, who ranged in age from one to six years old, for 23 weeks after treatment. While the gene therapy did not give the children a “normal” level of hearing, they went from not hearing anything under 95 decibels—about as loud as a food processor or motorcycle—to perceiving sounds of around 45 decibels—the level of a typical conversation or the hum of a refrigerator. Other children in the study had previously received a cochlear implant in one ear and had already learned to speak. In those cases, doctors injected the gene therapy into their other ear. Cochlear implants are surgically implanted devices that stimulate the auditory nerve to provide a sense of sound to its wearer. The implants don’t reproduce natural hearing, though.

The resulting sound can be robotic or distorted. And when they’re switched off, the wearer can’t hear at all. With gene therapy, researchers are aiming to provide a natural sense of hearing. When they followed up with patients after the injection, they turned off the cochlear implants to assess how well the therapy was working in the children. Several companies are pursuing gene therapies for this same cause of deafness.  Scientists have been interested in restoring otoferlin for years but have struggled with how to get the gene inside virus particles. The otoferlin gene is large—about 6,000 DNA letters long—and doesn’t fit into the viruses used for gene therapy. Scientists eventually figured out they could split the gene in two and deliver the pieces separately. When tested in mice, the gene came together in the inner ear and allowed them to hear. The team from Fudan University and Mass Eye and Ear think their otoferlin gene therapy will be able to provide sound perception to people with an otoferlin mutation at any age, but they believe giving it in the first few years of life—a critical time for brain development—will be better for speech and language acquisition. They plan to expand the trial to more patients and continue to follow their outcomes over a longer period.

Source: WIRED