A new gene therapy tested in China significantly improved hearing in children and adults with a rare inherited form of deafness, according to interim results from a multicenter clinical trial.
The treatment used an engineered virus to deliver a working copy of a faulty gene and was found to be safe, with measurable improvements in hearing within weeks.
Investigators enrolled 10 participants, including 9 aged 1.5 to 23.9 years, all of whom had autosomal recessive deafness type 9 (DFNB9) caused by mutations in the OTOF gene. OTOF encodes otoferlin, a protein essential for transmitting sound from the inner ear to the brain. All participants had profound congenital hearing loss before treatment.
The therapy was delivered via a synthetic adeno-associated virus (AAV) vector (Anc80L65) injected into the cochlea. Seven participants received unilateral injections; three received bilateral. Hearing was assessed over 6 to 12 months using pure-tone audiometry, auditory brainstem response (ABR), and auditory steady-state response (ASSR).
On average, pure-tone thresholds improved from 106 dB to 52 dB. Click-evoked ABR improved from 101 dB to 48 dB, tone-burst ABR from 91 dB to 57 dB, and ASSR from 80 dB to 64 dB.
Most hearing gains occurred within the first month. By that time, over 60% of the total improvement had already been achieved. While all age groups showed improvement, the most substantial gains were seen in children aged 5 to 8 years.
No serious adverse events were reported. Among the 162 documented events, all were mild or moderate. The most common were decreased neutrophil levels, elevated platelet counts, and anemia. One participant received two injections in the same ear, with no complications and further hearing improvement.
Hearing recovery varied. One 7-year-old child achieved near-normal hearing by 12 months and could recognize speech without lipreading. The adult participant, aged 23.9, improved from 101 dB to 70 dB.
Response to therapy appeared age-dependent. Children aged 5 to 8 had the best outcomes, while infants under 2 and adults had more modest improvements. These findings suggested a potential optimal treatment window, but further studies are needed.
The study remains ongoing to assess long-term safety and durability.
Full disclosures can be found in the study.
Source: nature medicine