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...