A gene therapy study published recently in the journal Nature Medicine showed promising results in restoring hearing in patients of all ages with genetic hearing loss and congenital deafness. The study involved ten patients aged 1 to 24, all of whom had a genetic form of deafness caused by mutations in the OTOF gene, with hearing improvement observed in all participants.
Mutations in the OTOF gene disrupt the production of the otoferlin protein, which plays a critical role in the auditory process by transmitting sound signals from the inner ear to the brain. This deficiency leads to profound hearing loss from birth. The researchers aimed to address this by delivering a functional version of the OTOF gene directly to the inner ear using a synthetic adeno-associated virus known as Anc80L65.
The therapy was administered via a single injection through the round window membrane, accessed through the trans-mastoid facial recess. This method allowed the gene therapy to target the affected cells precisely without the need for more invasive procedures.
On average, participants experienced an improvement in auditory threshold from 106 decibels—a level indicating profound deafness—to 52 decibels, approaching the level of normal conversation. Hearing improvements were measured using both objective brainstem response tests and behavioral hearing assessments, with a six-month follow-up showing improvement in all participants.
One case was that of a seven-year-old girl who completely restored her hearing and began to speak freely just four months after the treatment, engaging in everyday conversations with her mother. Adults also demonstrated sustained improvement in hearing, though to a lesser extent compared to children. Improvements were observed in adolescents and adults, including a participant nearly 24 years old.
The therapy worked best in children, particularly those aged 5 to 8 years, who showed improvement in their ability to communicate. However, even younger children and older participants showed improvement, indicating the potential of gene therapy across a wide age range.
"This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults," said Dr. Maoli Duan, a consultant and lecturer at the Department of Clinical Science, Intervention and Technology at the Karolinska Institutet, according to a press release published on EurekAlert.
The gene therapy was well tolerated by all participants, with minimal side effects and no serious complications reported during the study. The most common adverse reaction was a mild decrease in certain white blood cells, but this did not result in any health issues.
The success of the trial marks a milestone in the treatment of genetic deafness and is considered one of the first steps towards treating cases of genetic deafness using gene therapy. The researchers believe that OTOF-related deafness is just the beginning for gene therapy applications in hearing loss. They are expanding their work to target other, more common genes that cause deafness, such as GJB2 and TMC1.
Dr. Duan expressed hope that the study will pave the way for gene therapies that treat more common forms of genetic hearing loss. "We will now be following these patients to see how lasting the effect is," he said. The team plans to monitor the participants for at least five to ten years to determine the long-term efficacy and safety of the treatment.
The findings reveal insights into the ideal window for treatment, with children between the ages of five and eight showing the most pronounced benefit. The reasons for the varying levels of improvement across different ages are not yet fully understood, but the study suggests that the brain's ability to process newly restored sounds may play a role.
Cochlear implants have long been the primary treatment option for individuals with profound hearing loss, but they require invasive surgery and cannot fully replicate the nuance of natural hearing. The gene therapy offers a less invasive alternative that has the potential to restore natural hearing by addressing the underlying genetic cause.
The preparation of this article relied on a news-analysis system.