Audiological characteristics following gene therapy in patients with autosomal recessive deafness 9.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-05-09 DOI:10.1016/j.medj.2025.100696

Longlong Zhang, Dingding Dong, Yanbo Yin, Honghai Tang, Jun Lv, Qi Cao, Wuqing Wang, Bing Chen, Yunfeng Wang, Huawei Li, Daqi Wang, Yilai Shu

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引用次数: 0

Abstract

Background: Gene therapy shows promising potential for patients with autosomal recessive deafness 9 (DFNB9), with ongoing clinical trials (ChiCTR2200063181). A deeper understanding of changes in audiological characteristics is crucial for optimizing the monitoring and evaluation of patients' recovery post-treatment.

Methods: Audiological data were collected from 10 DFNB9 patients who underwent gene therapy, including auditory brain stem response (ABR), auditory steady-state response (ASSR), distortion product otoacoustic emission (DPOAE), and pure-tone audiometry (PTA) tests.

Findings: A clear ABR wave V was observed in all participants by 13 weeks. By 52 weeks, distinct ABR waves I and III were visible in some participants. The 1-kHz ABR wave V latency at 85 dB decreased significantly from 9.220 (range 9.015-9.810) ms at 4 weeks to 8.190 (range 7.780-8.530) ms at 52 weeks (p = 0.004), with a trend toward increased wave V amplitude (p = 0.055). Significant correlations were observed between PTA, ABR, and ASSR thresholds at 0.5-4 kHz. The DPOAE signal-to-noise ratio (SNR) at 26 weeks post-treatment showed no significant difference compared with pre-treatment SNR values, nor were there significant correlations between the pre-treatment SNR values and the post-treatment ABR thresholds.

Conclusions: The study demonstrates that ABR and ASSR are reliable objective tools for assessing hearing recovery in DFNB9 patients after gene therapy. ABR reveals positive changes in the auditory pathway over time after gene therapy, enhancing our understanding of the impact of gene therapy on auditory pathway recovery.

Funding: This work was funded by the National Natural Science Foundation of China.

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常染色体隐性耳聋患者基因治疗后的听力学特征分析

背景：正在进行的临床试验（ChiCTR2200063181）显示，基因治疗对常染色体隐性耳聋9 （DFNB9）患者有很大的潜力。深入了解听力学特征的变化对于优化患者治疗后康复的监测和评估至关重要。方法：收集10例接受基因治疗的DFNB9患者的听力学数据，包括听觉脑干反应（ABR）、听觉稳态反应（ASSR）、畸变产物耳声发射（DPOAE）和纯音听力学（PTA）测试。结果：13周时，所有受试者均观察到清晰的ABR V波。到52周时，在一些参与者中可以看到明显的ABR波I和III。85 dB时1 khz ABR波V潜伏期从4周时的9.220 (9.015-9.810)ms显著降低至52周时的8.190 (7.780-8.530)ms (p = 0.004)，波V振幅呈增加趋势（p = 0.055）。在0.5-4 kHz时，PTA、ABR和ASSR阈值之间存在显著相关性。治疗后26周DPOAE信噪比（SNR）与治疗前无显著差异，治疗前SNR值与治疗后ABR阈值无显著相关性。结论：本研究表明ABR和ASSR是评估基因治疗后DFNB9患者听力恢复的可靠客观工具。ABR揭示了基因治疗后听觉通路随时间的积极变化，增强了我们对基因治疗对听觉通路恢复影响的理解。基金资助：本工作由国家自然科学基金资助。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.