Gene therapy led to faster gains in hearing and speech among children with congenital deafness compared with cochlear implants, according to a new cohort study of 72 patients. Conducted between December 28, 2022, and November 30, 2024, at a tertiary hospital in China, the study evaluated children with severe to complete hearing loss due to OTOF gene variants.
Eleven children received gene therapy (mean age 3.7 years), and 61 received cochlear implants (mean age 1.9 years). All participants were aged 1 to 18 years and were matched based on hearing level, speech ability, and duration of deafness before treatment, though the comparison groups varied by time point and analysis type.
At 6 months, children who received gene therapy showed better auditory and speech perception scores. On the IT-MAIS/MAIS scale, which measures meaningful auditory integration, the median score was 31 in the gene therapy group compared with 23.5 in the cochlear implant group (P = .01). At 12 months, this advantage persisted (32 vs 28; P = .007).
Mismatch negativity testing, used to assess auditory information processing, showed shorter latencies in gene therapy patients at 6 months (median, 0.20 seconds vs 0.23 seconds; P = .006), indicating faster neural processing of sound.
Gene therapy restored auditory brainstem response thresholds from more than 95 dB nHL at baseline to 54.8 dB nHL at 12 months in 9 patients. However, the study found that cochlear implant patients achieved significantly better hearing thresholds at 12 months overall, despite gene therapy patients showing earlier improvements at 6 months.
Children with gene therapy in one ear and a cochlear implant in the opposite ear (bimodal group) also performed better in certain specialized tasks. In speech-in-noise testing, their disyllable speech reception threshold was −1.0 dB sound pressure level compared to 5.3 dB SPL in unilateral cochlear implant patients (P = .03). In music perception, the bimodal group had higher in-tune singing rates (66.6% vs 37.1%; P = .04) compared to bilateral cochlear implant patients.
The study had significant limitations, including its small sample size and the inability of some young children to complete objective tests. Gene therapy patients were followed prospectively at multiple intervals, while cochlear implant patients received only single-time assessments, potentially introducing bias in data collection. Most importantly, the gene therapy studied targets only OTOF gene variants, which represent a small subset of congenital deafness cases, severely limiting the generalizability of results.
The authors noted that both treatments showed comparable auditory and speech perception at 3 months, with gene therapy's main advantages appearing at 6 months. Cochlear implants remain the standard treatment for the vast majority of hearing loss cases, especially when gene therapy is not available for the specific genetic cause.
"Our results showed that GT, as a novel and cutting-edge intervention, is better than CI in auditory speech perception in noise and music perception, which could become the first choice for treating congenital deafness caused by OTOF variants," wrote Xiaoting Cheng from the ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, China, and colleagues.
The authors recommended larger studies with standardized prospective follow-up in both treatment groups and evaluation across different genetic causes of deafness. They emphasized that longer-term research is needed to understand the durability, safety, and broader applicability of gene therapy in clinical practice.
Full disclosures can be found in the published study.
Source: JAMA Neurology
