Journal article
A longitudinal and cross‐sectional study of plasma neurofilament light chain concentration in Charcot‐Marie‐Tooth disease
Journal of the peripheral nervous system, Vol.27(1), pp.50-57
12/2021
DOI: 10.1111/jns.12477
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 years 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 GARSC201R mice. There was no significant difference in plasma NFL in GARSP278KY 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.
Details
- Title: Subtitle
- A longitudinal and cross‐sectional study of plasma neurofilament light chain concentration in Charcot‐Marie‐Tooth disease
- Creators
- A M Rossor - Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, Queen Square London UKM Kapoor - Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, Queen Square London UKH Wellington - Department of Neurodegenerative Disease UCL Institute of Neurology London UK, UK Dementia Research Institute at UCL London UKE L Spaulding - Jackson LaboratoryJ N Sleigh - Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, Queen Square London UK, UK Dementia Research Institute at UCL London UKR W Burgess - Jackson LaboratoryM Laura - Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, Queen Square London UKH Zetterberg - Sahlgrenska University HospitalA Bacha - University of IowaX Wu - University of IowaA Heslegrave - Department of Neurodegenerative Disease UCL Institute of Neurology London UK, UK Dementia Research Institute at UCL London UKM E Shy - University of IowaM M Reilly - Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, Queen Square London UK
- Resource Type
- Journal article
- Publication Details
- Journal of the peripheral nervous system, Vol.27(1), pp.50-57
- DOI
- 10.1111/jns.12477
- ISSN
- 1085-9489
- eISSN
- 1529-8027
- Grant note
- DOI: 10.13039/501100000374, name: British Medical Association; DOI: 10.13039/100010663, name: H2020 European Research Council, award: #681712, 860197; DOI: 10.13039/501100004359, name: Vetenskapsrådet, award: #2018‐02532; DOI: 10.13039/501100013913, name: International Nut and Dried Fruit Council; DOI: 10.13039/100002721, name: Charcot-Marie-Tooth Association; DOI: 10.13039/100005202, name: Muscular Dystrophy Association, award: MDA510281; DOI: 10.13039/501100007155, name: Medical Research Council Canada, award: MRC MR/S005021/1; DOI: 10.13039/100010269, name: Wellcome Trust; DOI: 10.13039/100002565, name: Alzheimer's Drug Discovery Foundation, award: #201809‐2016862
- Language
- English
- Date published
- 12/2021
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984199858902771
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