Cornelissen Laura, Donado Carolina, Yu Timothy W, Berde Charles B
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, United States.
Department of Anaesthesia, Harvard Medical School, Boston, MA, United States.
Front Neurol. 2022 Feb 10;13:664710. doi: 10.3389/fneur.2022.664710. eCollection 2022.
Several neurological disorders may be amenable to treatment with gene-targeting therapies such as antisense oligonucleotides (ASOs) or viral vector-based gene therapy. The US FDA has approved several of these treatments; many others are in clinical trials. Preclinical toxicity studies of ASO candidates have identified dose-dependent neurotoxicity patterns. These include degeneration of dorsal root ganglia, the cell bodies of peripheral sensory neurons. Quantitative sensory testing (QST) refers to a series of standardized mechanical and/or thermal measures that complement clinical neurologic examination in detecting sensory dysfunction. QST primarily relies on patient self-report or task performance (i.e., button-pushing). This brief report illustrates individualized pragmatic approaches to QST in non-verbal subjects receiving early phase investigational intrathecal drug therapies as a component of clinical trial safety protocols. Three children with neurodevelopmental disorders that include , and are presented. These case studies discuss individualized testing protocols, accounting for disease presentation, cognitive and motor function. We outline specific considerations for developing assessments for detecting changes in sensory processing in diverse patient groups and safety monitoring trials of early phase investigational intrathecal drug therapies. QST may complement information obtained from the standard neurologic examination, electrophysiologic studies, skin biopsies, and imaging. QST has limitations and challenges, especially in non-verbal subjects, as shown in the three cases discussed in this report. Future directions call for collaborative efforts to generate sensory datasets and share data registries in the pediatric neurology field.
几种神经系统疾病可能适合用基因靶向疗法进行治疗，如反义寡核苷酸（ASO）或基于病毒载体的基因疗法。美国食品药品监督管理局（FDA）已批准了其中几种治疗方法；还有许多其他疗法正在进行临床试验。ASO候选药物的临床前毒性研究已确定了剂量依赖性神经毒性模式。这些包括背根神经节（外周感觉神经元的细胞体）的退化。定量感觉测试（QST）是指一系列标准化的机械和/或热测量方法，可在检测感觉功能障碍时补充临床神经学检查。QST主要依赖患者的自我报告或任务表现（即按键）。本简要报告阐述了在接受早期鞘内药物治疗作为临床试验安全方案一部分的非语言受试者中，QST的个体化实用方法。介绍了三名患有神经发育障碍（包括 、 和 ）的儿童。这些案例研究讨论了个体化测试方案，考虑了疾病表现、认知和运动功能。我们概述了在不同患者群体中开发用于检测感觉处理变化的评估方法以及早期鞘内药物治疗安全性监测试验的具体注意事项。QST可补充从标准神经学检查、电生理研究、皮肤活检和影像学获得的信息。QST有局限性和挑战，尤其是在非语言受试者中，如本报告所讨论的三个案例所示。未来的方向需要各方共同努力，以生成感觉数据集并在儿科神经病学领域共享数据登记库。
