Gene therapy brings back hearing in real-world clinical trial

Scientists have achieved a major milestone in the treatment of congenital deafness. A new study reports that gene therapy has successfully restored hearing in both children and young adults born with OTOF-linked hearing loss. The treatment produced rapid, meaningful results, and no serious side effects were observed.

The trial used a modified virus to deliver a working version of the OTOF gene directly into the inner ear. This gene produces otoferlin, a protein essential for transmitting sound signals to the brain. When it's missing or mutated, individuals are born completely deaf. Fixing this gene rewires the body’s ability to hear.

Treatment Delivered Through a Single Injection

Researchers used an engineered virus known as Anc80L65 to carry the OTOF gene into the cochlea, specifically at its base. Just one injection into the inner ear was enough to restart sound transmission. Once inside, cells began producing otoferlin, enabling them to pass sound signals from the ear to the brain once again.

The therapy had been successfully tested in mice and nonhuman primates before human trials were approved. Those early lab studies paved the way for this small, multicenter clinical trial conducted in five hospitals across China.

Did you know?
The OTOF gene produces otoferlin, a protein crucial for transmitting sound signals. When it malfunctions, people are born completely deaf despite having otherwise intact inner ear structures.

Strong Hearing Gains in Patients of All Ages

Ten patients between toddler age and their early twenties participated. All had OTOF mutations. Following the gene injection in one or both ears, several patients showed restored hearing within weeks. On average, patients' hearing thresholds improved dramatically, from 106 decibels to 52 decibels.

Tests such as the click auditory brainstem response (ABR), tone-burst ABR, and auditory steady-state response all indicated clear hearing gains. The fastest and most dramatic improvements were seen in children, particularly those between ages five and eight.

One seven-year-old girl regained nearly full hearing within four months and was soon having normal conversations with her family. Still, older participants also showed meaningful improvements, suggesting a broad treatment window.

Tolerable Side Effects, No Serious Risks Found

The treatment was well tolerated by all ten participants. Across the group, 162 side effects were recorded, mostly mild to moderate and temporary.

Some individuals experienced a drop in neutrophils, a specific type of white blood cell, but all symptoms resolved without complications. Importantly, no serious adverse events were noted during the six to twelve months of follow-up.

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A Global Collaborative Effort

The study was conducted through partnerships among institutions, including Zhongda Hospital at Southeast University and Karolinska Institutet in Sweden. One of the lead authors, Dr. Maoli Duan, hailed the results as a turning point for genetic hearing treatments.

"This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults," he said. "We will now be following these patients to see how lasting the effect is."

Next Steps: Expanding the Gene Therapy Horizon

Researchers stress that this is just the beginning. Future studies will explore gene therapies targeting other prevalent genetic hearing disorders, such as those involving the GJB2 and TMC1 genes. These will be more complex to treat, but early lab data is promising.

With long-term follow-up underway and larger trials planned, gene therapy for deafness is poised to redefine what’s possible in auditory medicine. For now, families affected by this form of inherited hearing loss have a new reason to hope and to hear.