a Department of Neurology , University of Miami , Miami , FL , USA and.
b Nuffield Department of Clinical Neurosciences , University of Oxford , Oxford , UK.
Amyotroph Lateral Scler Frontotemporal Degener. 2019 Aug;20(5-6):303-309. doi: 10.1080/21678421.2019.1587634. Epub 2019 Mar 20.
Successful treatment of neurodegenerative disease may hinge on early therapeutic intervention. This requires an understanding of early/pre-symptomatic disease, a need that is underscored by advances in antisense oligonucleotide, and viral-vector-based gene therapies. In amyotrophic lateral sclerosis (ALS), the study of pre-symptomatic disease requires a cohesive conceptual framework for describing this phase of disease. Informed by the literature in other neurodegenerative diseases and extensive personal experience, a model is proposed that distinguishes ALS as a clinical syndrome from ALS as a disease, and characterizes pre-symptomatic ALS as having two identifiable stages: pre-manifest and prodromal. The unique and critical importance of biomarker development is articulated and an operational definition of phenoconversion is provided. It is hoped that this framework will accelerate collective efforts to study pre-symptomatic ALS, and aid in the design and implementation of an early intervention- or disease-prevention trial.
成功治疗神经退行性疾病可能取决于早期治疗干预。这需要了解早期/症状前疾病，反义寡核苷酸和基于病毒载体的基因治疗的进展突出了这一需求。在肌萎缩侧索硬化症 (ALS) 中，对症状前疾病的研究需要一个连贯的概念框架来描述疾病的这一阶段。根据其他神经退行性疾病的文献和广泛的个人经验，提出了一个模型，将 ALS 作为一种临床综合征与 ALS 作为一种疾病区分开来，并将症状前 ALS 特征化为具有两个可识别的阶段：前显型和前驱期。阐明了生物标志物开发的独特和关键重要性，并提供了表型转化的操作定义。希望这个框架将加速研究症状前 ALS 的集体努力，并有助于设计和实施早期干预或疾病预防试验。
