Breakthrough AAV Gene Therapy Restores Hearing in Children and Adults with Genetic Deafness

A groundbreaking new study, involving researchers from Karolinska Institutet in collaboration with hospitals and universities in China, reports significant success in improving hearing in individuals with congenital deafness or severe hearing impairment. The study demonstrates that gene therapy can restore hearing in patients with OTOF gene mutations, proving to be both effective and well-tolerated across a range of ages.

“This is a huge step forward in the genetic treatment of deafness, one that can be life-changing for children and adults,” states Dr. Maoli Duan, a corresponding author from Karolinska Institutet.

Targeting the Root Cause: OTOF Gene Mutations

The study included ten patients aged 1 to 24, all suffering from a genetic form of deafness caused by mutations in the OTOF gene. These mutations lead to a deficiency of the otoferlin protein, which is vital for transmitting auditory signals from the ear to the brain.

The Gene Therapy Approach

The therapeutic strategy involved:

• AAV Delivery: A synthetic adeno-associated virus (AAV) was used as a vector to deliver a functional version of the OTOF gene directly to the inner ear.
• Single Injection: The gene therapy was administered via a single injection through the round window membrane at the base of the cochlea.

Rapid and Significant Hearing Improvement

The treatment showed rapid effects, with the majority of patients recovering some hearing within just one month. A six-month follow-up revealed substantial hearing improvement across all participants, with the average perceptible sound volume improving dramatically from 106 decibels to 52 decibels.

Key Observations:

• Best Results in Children: Younger patients, particularly those between five and eight years old, showed the most significant response. One seven-year-old girl regained almost all her hearing, enabling her to engage in daily conversations within four months.
• Efficacy in Adults: Crucially, the therapy also proved effective in teenagers and adults, expanding its potential reach.

Safety and Future Outlook

The study reported that the gene therapy was safe and well-tolerated, with no serious adverse reactions during the 6 to 12-month follow-up period. The most common adverse event was a transient reduction in neutrophil count.

Dr. Duan emphasized that “OTOF is just the beginning.” Researchers are now expanding their work to target other, more common genes associated with deafness, such as GJB2 and TMC1, with promising preclinical results. This breakthrough offers strong confidence that a wide range of genetic deafness conditions may one day be treatable.

The study was a collaborative effort with institutions in China and received funding from Chinese research programs and Otovia Therapeutics Inc., the company that developed the gene therapy.