Gene therapy single-time recovery of hearing in deaf people

Single injection gene therapy has restored hearing in all ten congenital deaf patients, marking a significant advance in the treatment of genetic hearing loss.

This treatment is conducted from the ages of young children to adults, with some patients returning to almost normal hearing within a few months. The study, published in Nature Medicine, shows that gene therapy can quickly repair the molecular mechanisms required for sound transmission from the ear to the brain.

Patients aged between 1.5 and 24 years old all have mutations in the OTOF gene, which prevents the production of Otoferlin, a protein necessary to transmit auditory signals. The researchers used modified viruses to deliver functional copies of the gene directly into the inner ear, achieving significant hearing improvements that began within a few weeks.

Rapid recovery across age groups

The results exceeded expectations for speed and range. “This is a huge step in genetic treatment of deafness, which can make life-changing for children and adults,” explained Maori Duan, a corresponding author of the Karolinska Institutet.

The treatment takes effect very quickly, and most patients show hearing improvements within a month. On average, the patient’s hearing threshold increased from 106 decibels (equal to deep deafness, etc.) to 52 decibels, making the range of many decibels possible.

A seven-year-old girl received her most dramatic recovery, having almost all her hearing and conversations with her mother almost four months after treatment. The study also demonstrates that gene therapy can work in adolescents and adults, a population that has never accepted this approach.

Key treatment outcomes

Multicenter trials at five Chinese hospitals reveal several important findings:

• All ten patients had significant hearing improvements within six months
• 62% of total hearing recovery occurs within the first month of treatment
• Children aged 5-8 show the best response to treatment
• No serious adverse reactions occurred during the 6-12-month follow-up period
• One patient received two injections safely, opening up the possibility of booster treatment

Precision drugs at the molecular level

The treatment targets autosomal recessive deafness 9 (DFNB9), which is caused by mutations that destroy the auricular cordon. The protein acts like a molecular Velcro, which helps detect neurotransmitters released by hair cells that carry auditory signals to the brain. Without functional ear tongues, the patient can have intact hair cells but cannot transmit sound information.

The researchers used a synthetic adeno-associated virus called ANC80L65 to deliver therapeutic genes through a circular window membrane through a single injection into the cochlea. The process performed under microscopic guidance takes advantage of the virus’s natural ability to infect inner ear cells and deposit genetic material.

International cooperation involves researchers in China working with experts from Karolinska Institutet. “Smaller studies in China have previously shown positive results in children, but this is the first time the method has been tested in adolescents and adults,” Dr. Duan noted.

Age-related reaction reveals the best window

Perhaps most interestingly, the study found an age-dependent pattern of treatment effectiveness. Although all patients improved, patients between the ages of 5-8 achieved the best results – with the best results than younger toddlers and older participants.

This finding challenges the hypothesis that young patients should always respond better to gene therapy. The researchers speculate that although the exact mechanism is unclear, factors such as surgical accuracy, inner ear development, or viral transduction efficiency may change with age.

It turns out that this treatment is safe for all ages, with the most common side effect being a temporary reduction in leukocyte count. No serious adverse reactions occurred even in patients who received a second injection with moderate initial results.

Going forward, researchers plan to expand their work to other genetic causes of deafness. “OTOF is just the beginning,” Dr. Duan said. “We and other researchers are expanding our work to other more common genes that cause deafness, such as GJB2 and TMC1.”

It is estimated that 1.5 billion people worldwide experience hearing loss, and this genetic approach provides hope for therapeutic conditions and was once considered permanently irreversible. The rapid recovery schedule (the biggest benefit of appearing within the first month) is that gene therapy may become a practical clinical option for appropriate selection of patients with genetic hearing loss.

Related