Can Genetic Deafness Be Cured? 24-Year-Old Hears For The First Time With New Therapy

Scientists have tested a new gene therapy to treat genetic deafness in children and young people up to 24 years old. The treatment, using a modified virus that corrects the defective gene in the ear, was safe and showed significant improvement in hearing in most participants in just one month. The best results were seen in children between 5 and 8 years old. The study is still ongoing, but the initial results are very promising.

Congenital hearing loss, which affects children from birth, can have several genetic causes. Among them is autosomal recessive deafness type 9, caused by mutations in the OTOF gene. This gene is essential for the proper functioning of the sensory cells of the cochlea, a structure in the inner ear responsible for transforming sound into electrical signals for the brain.

In recent years, gene therapy, a technique that seeks to correct defective genes, has shown promising results in treating this form of deafness, especially in young children. However, there are still doubts about the effectiveness and safety of this treatment in older people.

With this in mind, researchers conducted a clinical trial in China with ten participants, aged between 1.5 and 23.9 years, all diagnosed with the same genetic condition. The therapy used consisted of introducing a functional copy of the OTOF gene using a viral vector called AAV (adeno-associated virus), a technology already known for its safety in other therapies.

The modified virus acts as a "carrier" that delivers the correct gene directly to the cells in the ear. All participants received the treatment in only one ear.

The main objective of the study was to assess whether the treatment would be safe and well tolerated over 5 years. So far, after a follow-up of 6 to 12 months, the initial results are encouraging: there were no serious side effects.

There were 162 mild or moderate adverse events (grades I and II), the most common being a slight reduction in the number of neutrophils (a type of immune system cell), observed in 16 cases. One of the patients received two applications of the treatment to investigate the effects of this repetition.

Most importantly, all participants showed significant improvement in hearing. The average hearing level (measured by the pure tone threshold) improved from about 106 decibels (indicating profound deafness) to 52 decibels, which may represent a significant functional improvement, allowing the perception of everyday sounds.

Other tests that evaluate the electrical activity of the auditory nerve and brain (such as the ABR and the auditory steady-state response) also showed consistent improvements. Hearing tests such as the click ABR and the burst-tone ABR are tests that measure how the brain responds to sounds.

In ABR (Auditory Brainstem Response), small electrodes placed on the head record the electrical activity of the auditory nerve and brain in response to sound stimuli. Click ABR uses short, rapid sounds (clicks), while tone-burst ABR uses more specific sounds at different frequencies.

These tests are essential for assessing hearing, especially in people who cannot actively respond, such as infants or unconscious patients.

ABR test, which assesses the electrical activity of the auditory nerve and brain.

The researchers found that most of the hearing improvement occurred within the first month after the therapy was administered, indicating a relatively rapid effect. In addition, some hearing tests, such as the click ABR and the tone burst ABR, were able to predict with good accuracy which patients would have the best hearing results after four months, which may help guide future treatments.

Interestingly, the age of the participants was affected: children between the ages of 5 and 8 had the most positive responses, suggesting that there is an ideal “window of opportunity” to apply gene therapy and obtain the best results.

However, improvements were also seen in older patients, which is encouraging. In summary, this study provides some of the strongest evidence to date that gene therapy for genetic deafness can be safe and effective in humans, even outside of early childhood. Although the results are still preliminary and follow-up is ongoing, they mark an important advance in the treatment of genetic hearing loss and offer hope to many families.

READ MORE:

AAV gene therapy for autosomal recessive deafness 9: a single-arm trial

Jieyu Qi, Liyan Zhang, Ling Lu, Fangzhi Tan, Cheng Cheng, Yicheng Lu, Wenxiu Dong, Yinyi Zhou, Xiaolong Fu, Lulu Jiang, Chang Tan, Shanzhong Zhang, Sijie Sun, Huaien Song, Maoli Duan, Dingjun Zha, Yu Sun, Xia Gao, Lei Xu, Fan-Gang Zeng, and Renjie Chai 

Nature Medicine (2025)

https://doi.org/10.1038/s41591-025-03773-w

Abstract: 

Gene therapy for congenital deafness has shown promising results in children but lacks data in older populations. We conducted a single-arm trial of adeno-associated virus (AAV)-OTOF gene therapy using the Anc80L65 capsid in ten participants with autosomal recessive deafness 9 aged 1.5 to 23.9 years at five sites in China. The primary endpoints were safety and tolerability within 5 years, and secondary endpoints assessed auditory function. Initial findings from the ten patients with 6–12 months of follow-up, including one patient who received two injections, revealed that the therapy was well tolerated, with 162 grade I/II adverse events. Decreased neutrophil percentage was the most common event (16 of 162). All ten participants had at least 6 months of follow-up and improved their pure-tone-average hearing level from baseline 106 ± 9 (mean ± s.d.) to 52 ± 30 decibels (dB). Other secondary endpoints showed similar improvements, including the average click auditory brainstem response (ABR) threshold, the tone-burst ABR threshold and the auditory steady-state response (101 ± 1 to 48 ± 26 dB, 91 ± 4 to 57 ± 19 dB and 80 ± 14 to 64 ± 21 dB, respectively). Post hoc analyses were conducted to evaluate the timecourse and factors contributing to the hearing improvement. Therapeutic effect was rapid, taking 1 month to achieve most of the overall hearing improvement. On an individual level, click and tone-burst ABR thresholds, but not the auditory steady-state response, reliably predicted the behavioral pure-tone-average thresholds after 4 months (R2 = 0.68, 0.73 and 0.17, respectively). An age-dependent therapeutic effect was observed, with optimal outcomes in 5- to 8-year-olds. These preliminary results show that AAV-OTOF was safe and well tolerated in patients ranging from toddlerhood to adulthood. The trial remains ongoing and requires extended follow-up to confirm the long-term safety and efficacy. ClinicalTrials.gov registration: NCT05901480.