In recent years, gene therapy has emerged as a promising treatment for genetic forms of congenital deafness—hearing loss that’s present at birth—in children. A new study shows that gene therapy can bestow hearing in teenagers and adults with this condition, too.
The study, published Wednesday in the journal Nature Medicine, recruited patients with deafness or severe hearing impairment caused by mutations in the OTOF gene. This gene manufactures a protein called Otoferlin, which plays a critical role in transmitting signals from the ear to the brain. Roughly 200,000 people worldwide are deaf due to a mutation in the OTOF gene. Over the past several years, gene therapies have successfully improved hearing in children with OTOF-linked deafness, but few studies have investigated their efficacy in teenagers and adults with this condition.
The authors of this new study sought to fill that gap. Researchers at the Karolinska Institute in Sweden administered gene therapy to 10 patients between the ages of 1 and 24 across five hospitals in China, all of whom had a genetic form of deafness or severe hearing impairment caused by OTOF mutations. The treatment involved a single injection through a membrane at the base of the cochlea, a fluid-filled, spiral-shaped cavity inside the inner ear. This injection delivered a functional version of the OTOF gene via an engineered virus.
Just one month after the treatment, the majority of patients gained some hearing. Six months later, all 10 showed considerable hearing improvement, with the average volume of perceptible sound improving from 106 decibels (very loud) to 52 (much fainter). What’s more, the patients did not report any adverse side effects within the first 12 months post-treatment.
“This is very, very exciting,” co-author Maoli Duan, a consultant and docent in the Karolinska Institute’s Department of Clinical Science, Intervention, and Technology, told Gizmodo. Duan and his colleagues found the treatment to be most effective in young children, particularly those between the ages of 5 and 8 years old, who made up the majority of participants. One patient, a 7-year-old girl who received gene therapy in one ear and had a cochlear implant in the other, recovered almost all of her hearing. Just four months after treatment, she was able to hold daily conversations with her mother. When the two of them got caught in a storm one day, the girl told her mother she could hear the sound of rain for the first time, Duan told Gizmodo.
Previous gene therapy studies have shown similarly promising results in young patients with OTOF-linked deafness, Lawrence Lustig, a neurotologist at Columbia University Irving Medical Center who was not involved in the study, told Gizmodo. But seeing improvement in the two participants over the age of 12—who were 14 and 24 years old, respectively—surprised him.
“I think most of us thought going into this that the older you are, the worse the hearing results are going to be,” Lustig said. Some studies have shown that kids as old as 12 can gain some hearing improvement through OTOF gene therapy, “but I don’t think anyone’s seen anything [in patients] as old as 24 years,” he added. Still, future research will need to validate the efficacy of gene therapy in teenagers and adults with OTOF-linked deafness, as this small study only included two participants within this age range.
Duan and his colleagues plan to follow these patients for at least five to 10 years to determine whether the treatment remains effective over the long term. Though OTOF gene therapy still has a long way to go before it becomes available, these early results add to a growing body of evidence that points to its efficacy. Duan hopes this study will also pave the way for gene therapies that treat more common forms of genetic hearing loss.
“OTOF is just the beginning,” he said in a statement. “We and other researchers are expanding our work to other, more common genes that cause deafness, such as GJB2 and TMC1. These are more complicated to treat, but animal studies have so far returned promising results. We are confident that patients with different kinds of genetic deafness will one day be able to receive treatment.
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