Mutant huntingtin and neurofilament light have distinct longitudinal dynamics in Huntington’s disease
Year: 2020
Type: article
Study design: Observational Study
Abstract: The longitudinal dynamics of the most promising biofluid biomarker candidates for Huntington's disease (HD)-mutant huntingtin (mHTT) and neurofilament light (NfL)-are incompletely defined. Characterizing changes in these candidates during disease progression could increase our understanding of disease pathophysiology and help the identification of effective therapies. In an 80-participant cohort over 24 months, mHTT in cerebrospinal fluid (CSF), as well as NfL in CSF and blood, had distinct longitudinal trajectories in HD mutation carriers compared with controls. Baseline analyte values predicted clinical disease status, subsequent clinical progression, and brain atrophy, better than did the rate of change in analytes. Overall, NfL was a stronger monitoring and prognostic biomarker for HD than mHTT. Nonetheless, mHTT has prognostic value and might be a valuable pharmacodynamic marker for huntingtin-lowering trials.
Source: Science Translational Medicine
Authors: Filipe B. Rodrigues, Lauren M. Byrne, Rosanna Tortelli, Eileanoir B. Johnson, Peter A. Wijeratne, Marzena Arridge, Enrico De Vita, Naghmeh Ghazaleh, Richard Houghton, Hannah Furby, Daniel C. Alexander, Sarah J. Tabrizi, Scott Schobel, Rachael I. Scahill, Amanda Heslegrave, Henrik Zetterberg, Edward J. Wild
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Huntington's Disease Society of America, Hereditary Disease Foundation, Roche, CHDI Foundation, F. Hoffmann-La Roche, Wellcome Trust, Alzheimer's Society, National Institute for Health and Care Research, Svenska Forskningsrådet Formas, Alzheimer’s Research UK, Vetenskapsrådet, Innovative Medicines Initiative, Alzheimer’s Society, UK Dementia Research Institute, Horizon 2020 Framework Programme, Medical Research Council, Engineering and Physical Sciences Research Council, European Research Council, Centre For Medical Engineering, King’s College London
Awards: G1054121244, G1247657515, King's College London Medical Engineering Centre of Research Excellence, G2172654960, TREAT-HD: targeting neurodegeneration in Huntington's disease, G2417159676, TREAT-HD: targeting neurodegeneration in Huntington's disease, G5296857752, King's College London Medical Engineering Centre of Research Excellence, G6868616705, G7329585684, G8303168876, G8540753752, G8775246936, G938335843, G961285871
OpenAlex ID: W3112958994