Gene Therapy vs Cochlear Implantation in Restoring Hearing Function and Speech Perception for Individuals With Congenital Deafness - PubMed (original) (raw)

Comparative Study

. 2025 Sep 1;82(9):941-951.

doi: 10.1001/jamaneurol.2025.2053.

Xiaoting Cheng 1 2 3 4 5, Jiake Zhong 1 2 3 4 5, Jiajia Zhang 1 2 3 4 5, Chong Cui 1 2 3 4 5, Luoying Jiang 1 2 3 4 5, Yang-Wenyi Liu 1 2 3 4 5, Yuxin Chen 1 2 3 4 5, Qi Cao 1 2 3 4 5 6, Daqi Wang 1 2 3 4 5, Guiqing Cheng 1 2 3 4 5, Yuxin Zong 1 2 3 4 5, Chunxin Xu 7, Jun Lv 1 2 3 4 5, Hui Wang 1 2 3 4 5, Longlong Zhang 1 2 3 4 5, Biyun Zhu 1 2 3 4 5, Honghai Tang 1 2 3 4 5, Jinghan Wang 1 2 3 4 5, Xintai Fan 1 2 3 4 5, Yanqing Fang 1 2 3 4 5, Luo Guo 1 2 3 4 5, Jiawei Guo 1 2 3 4 5, Liheng Chen 1 2 3 4 5, Yanbo Yin 1 2 5, Zijing Wang 1 2 3 4 5, Lei Han 1 2 3 4 5, Shaowei Hu 1 2 3 4 5, Shengyi Wang 1 2 3 4 5, Guoyou Qin 8 9, Xuezhong Liu 10, Jinqiu Sang 11, Fangang Zeng 12, Wuqing Wang 1 2 3 4 5, Bing Chen 1 2 3 4 5, Zheng-Yi Chen 13 14, Huawei Li 1 2 3 4 5, Yilai Shu 1 2 3 4 5

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Comparative Study

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

Xiaoting Cheng et al. JAMA Neurol. 2025.

Erratum in

Abstract

Importance: 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.

Objective: To evaluate treatment outcomes in auditory and speech perception between patients with congenital deafness treated with GT, CI, or both.

Design, setting, and participants: 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.

Exposures: GT only vs CI; bimodal (unilateral GT plus contralateral CI) vs bilateral CI; GT (CI turned off [CI-off]) vs unilateral CI.

Main outcomes and measures: 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).

Results: 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).

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Zeng reported stock ownership in Nurotron and Axionics. Dr Z. Chen reported equity ownership in Salubritas Therapeutics. No other disclosures were reported.

References

    1. GBD 2019 Hearing Loss Collaborators . Hearing loss prevalence and years lived with disability, 1990-2019: findings from the Global Burden of Disease Study 2019. Lancet. 2021;397(10278):996-1009. doi: 10.1016/S0140-6736(21)00516-X -DOI -PMC -PubMed
    1. Morton CC, Nance WE. Newborn hearing screening—a silent revolution. N Engl J Med. 2006;354(20):2151-2164. doi: 10.1056/NEJMra050700 -DOI -PubMed
    1. van Zon A, Smulders YE, Stegeman I, et al. Stable benefits of bilateral over unilateral cochlear implantation after two years: a randomized controlled trial. Laryngoscope. 2017;127(5):1161-1168. doi: 10.1002/lary.26239 -DOI -PubMed
    1. Cardin V. Effects of aging and adult-onset hearing loss on cortical auditory regions. Front Neurosci. 2016;10:199. doi: 10.3389/fnins.2016.00199 -DOI -PMC -PubMed
    1. Ma SJ, Li SX, Tan H, et al. The mental health of paediatric cochlear implant recipients. J Laryngol Otol. 2024;138(5):487-495. doi: 10.1017/S0022215123001743 -DOI -PubMed

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