Gene Therapy vs Cochlear Implantation in Restoring Hearing Function and Speech Perception for Individuals With Congenital Deafness

OTOF gene therapy (GT) has been shown to improve hearing and speech. The efficacy of GT remains to be compared against cochlear implantation (CI), the current gold standard for congenital deafness. To evaluate treatment outcomes in auditory and speech perception between patients with congenital deafness treated with GT, CI, or both. This nonblind cohort study was conducted between December 2022 and November 2024. GT patients received follow-up at 3, 6, and 12 months; CI patients received 1-time evaluation at the corresponding time intervals or longer (3, 6, or 12 months). The study was conducted at a single class A tertiary hospital in China. Participants with congenital severe to complete hearing loss, aged 1 to 18 years, who received GT or CI were enrolled. They were matched on duration of deafness, hearing thresholds, and speech ability at the presurgical baseline. Of 1568 participants screened, 72 participants enrolled. Participants were excluded if they had inner ear malformations or vestibular-cochlear nerve abnormalities. GT only vs CI; bimodal (unilateral GT plus contralateral CI) vs bilateral CI; GT (CI turned off [CI-off]) vs unilateral CI. The primary outcomes were auditory and speech perception evaluated by questionnaires, including the Infant-Toddler Meaningful Auditory Integration Scale/Meaningful Auditory Integration Scale (IT-MAIS/MAIS), and tests, including audiometry, speech, and music tests. The main secondary outcome was auditory information processing ability assessed by mismatch negativity (MMN). A total of 11 GT patients (6 male [55%]; mean [SD] age at baseline, 3.7 [2.8] years) and 61 CI patients (34 male [56%]; mean [SD] age at baseline, 1.9 [1.5] years) were enrolled. The mean (SD) auditory brainstem response thresholds were restored from greater than 95.0 (0.0) decibels normalized hearing level (dB nHL) to 54.8 (15.9) dB nHL in 9 GT patients at 12 months. For GT-only vs CI in auditory and speech perception, GT patients performed better in IT-MAIS/MAIS at 6 months (median [IQR] score, 31.0 [30.0-32.0] vs 23.5 [19.0-26.3]; P = .01) and 12 months (median [IQR] score, 32.0 [31.0-32.0] vs 28.0 [24.5-30.5]; P = .007). GT patients showed shorter latencies of MMN at 6 months (median [IQR], 0.20 [0.05-0.21] seconds vs 0.23 [0.22-0.25] seconds; P = .006). For bimodal patients at 12 months, GT (CI-off) patients performed better than unilateral CI patients in speech in a noisy environment (median [IQR] disyllable, -1.0 [-3.0 to 2.4] dB sound pressure level (SPL) vs 5.3 [3.1 to 12.1] dB SPL; P = .03); GT plus CI patients performed better than bilateral CI patients in singing in-tune rates (median [IQR], 66.6% [53.7%-83.9%] vs 37.1% [30.3%-56.3%]; P = .04); GT plus CI patients showed shorter latencies of MMN at 12 months (median [IQR], 0.08 [0.07-0.10] seconds vs 0.21 [0.15-0.23] seconds, P = .01). GT patients showed stable hearing recovery and exhibited more rapid improvements in auditory and speech performance than CI patients, while outperforming CI patients in speech in noise performance and music perception. These findings suggest that GT may provide a novel effective treatment alternative for patients with genetically driven congenital deafness.