Validation of serum neurofilaments as prognostic & potential pharmacodynamic biomarkers for ALS

Objective. Identify preferred neurofilament assays, and clinically validate serum NfL and pNfH as prognostic and potential pharmacodynamic biomarkers relevant to ALS therapy development. Methods. Prospective, multi-center, longitudinal observational study of patients with ALS (n=229), primary lateral sclerosis (PLS, n=20) and progressive muscular atrophy (PMA, n=11). Biological specimens were collected, processed and stored according to strict standard operating procedures (SOPs) 1. Neurofilament assays were performed in a blinded manner by independent contract research organizations (CROs). Results. For serum NfL and pNfH measured using the Simoa assay, there were no missing data (i.e. both technical replicates below the lower limit of detection were not encountered). For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ~4% and ~10% of serum samples respectively. Mean coefficients of variation (CVs) for pNfH in serum and CSF were ~4-5% and ~2-3% res...研究目标：明确优选的神经丝检测方法，并对血清神经丝轻链蛋白（NfL）和磷酸化神经丝重链蛋白（pNfH）进行临床验证，以作为肌萎缩侧索硬化（ALS）疗法开发相关的预后生物标志物及潜在药效学生物标志物。 研究方法：本研究为针对肌萎缩侧索硬化（ALS，n=229）、原发性侧索硬化（PLS，n=20）及进行性肌萎缩（PMA，n=11）患者开展的前瞻性、多中心、纵向观察性研究。生物样本严格遵循标准操作规程（SOPs）¹进行采集、处理与储存。神经丝检测由独立合同研究组织（CROs）以盲法开展。 研究结果：采用Simoa检测法测得的血清NfL与pNfH无缺失数据（即未出现两次技术重复均低于检测下限的情况）。而采用Iron Horse及Euroimmun pNfH检测法时，分别有约4%和约10%的血清样本出现数据缺失。血清与脑脊液中pNfH的平均变异系数（CVs）分别约为4%-5%与2%-3%，res...