Document Type

Article

Publication Date

3-1-2022

Publication Title

Journal of the peripheral nervous system : JPNS

Keywords

JMG, Charcot-Marie-Tooth disease, biomarkers, neurofilament

JAX Source

J Peripher Nerv Syst . 2022 Mar;27(1):50-57.

Volume

27

Issue

1

First Page

50

Last Page

57

PMID

34851050

DOI

10.1111/jns.12477

Grant

British Medical Association (Vera Down); H2020 European Research Council, Grant/ Award Numbers: #681712, 860197; NIHR Biomedical Research Centre, University College London Hospital Biomedical Research Centre (Therapeutic Innovation Call for Neuroscience Theme); Swedish Research Council, Grant/Award Number: #2018-02532; the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases, Grant/Award Numbers: 1UOINS109403-01, R21TROO3034, U54NS065712; INC; the Charcot-Marie-Tooth Association (CMTA); Muscular Dystrophy Association, Grant/Award Number: MDA510281; Medical Research Council, Grant/Award Number: MRC MR/S005021/1; Wellcome Trust; the UK Dementia Research

Abstract

Advances in genetic technology and small molecule drug development have paved the way for clinical trials in Charcot-Marie-Tooth disease (CMT); however, the current FDA-approved clinical trial outcome measures are insensitive to detect a meaningful clinical response. There is, therefore, a need to identify sensitive outcome measures or clinically relevant biomarkers. The aim of this study was to further evaluate plasma neurofilament light chain (NFL) as a disease biomarker in CMT. Plasma NFL was measured using SIMOA technology in both a cross-sectional study of a US cohort of CMT patients and longitudinally over 6‚Äâyears in a UK CMT cohort. In addition, plasma NFL was measured longitudinally in two mouse models of CMT2D. Plasma concentrations of NFL were increased in a US cohort of patients with CMT1B, CMT1X and CMT2A but not CMT2E compared with controls. In a separate UK cohort, over a 6-year interval, there was no significant change in plasma NFL concentration in CMT1A or HSN1, but a small but significant reduction in patients with CMT1X. Plasma NFL was increased in wild type compared to GARS mice. There was no significant difference in plasma NFL in GARS compared to wild type mice. In patients with CMT1A, the small difference in cross-sectional NFL concentration vs healthy controls and the lack of change over time suggests that plasma NFL may lack sufficient sensitivity to detect a clinically meaningful treatment response in adulthood.

Comments

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium provided the original work is properly cited.

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