Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy.
Aged
Amyotrophic Lateral Sclerosis
/ blood
Animals
Biomarkers
/ blood
Bulbo-Spinal Atrophy, X-Linked
/ blood
Creatine Kinase
/ blood
Creatinine
/ blood
Disease Models, Animal
Female
Humans
Longitudinal Studies
Male
Mice
Middle Aged
Neurofilament Proteins
/ blood
Prospective Studies
Severity of Illness Index
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
12 03 2019
12 03 2019
Historique:
received:
12
08
2018
accepted:
05
11
2018
pubmed:
23
2
2019
medline:
18
12
2019
entrez:
22
2
2019
Statut:
ppublish
Résumé
To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal and bulbar muscular atrophy (SBMA) and can be used as biomarkers for disease severity. In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months. Blood NfL concentrations were increased in ALS samples, but were unchanged in both SBMA cohorts, were stable after 12 and 24 months, and were not correlated with clinical severity. Normal NfL levels were also found in a well-established mouse model of SBMA. Conversely, CK concentrations were significantly raised in SBMA compared with ALS samples, and were not correlated to the clinical measures. Creatinine concentrations were significantly reduced in SBMA, and strongly and significantly correlated with disease severity. While muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis. Creatinine, but not CK, correlated with disease severity, confirming its role as a valuable biomarker in SBMA.
Identifiants
pubmed: 30787165
pii: WNL.0000000000007097
doi: 10.1212/WNL.0000000000007097
pmc: PMC6511101
doi:
Substances chimiques
Biomarkers
0
Neurofilament Proteins
0
neurofilament protein L
0
Creatinine
AYI8EX34EU
Creatine Kinase
EC 2.7.3.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1205-e1211Subventions
Organisme : Medical Research Council
ID : MR/M008606/1
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : FRATTA/JAN15/946-795
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S006508/1
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : MALASPINA/APR13/817-791
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : TURNER/OCT15/972-797
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 205162/Z/16/Z
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
J Neurol Sci. 2008 Jan 15;264(1-2):100-5
pubmed: 17854832
Neurology. 2015 Jun 2;84(22):2247-57
pubmed: 25934855
Neurology. 2016 Sep 27;87(13):1329-36
pubmed: 27581216
J Neurol Neurosurg Psychiatry. 1982 Nov;45(11):1012-9
pubmed: 6890989
Cell Rep. 2016 Sep 27;17(1):125-136
pubmed: 27681426
PLoS One. 2012;7(7):e40998
pubmed: 22815892
Ann Clin Transl Neurol. 2016 Jun 23;3(7):537-46
pubmed: 27386502
Neurol Sci. 2016 Nov;37(11):1815-1821
pubmed: 27444956
Adv Exp Med Biol. 2018;1049:103-133
pubmed: 29427100
Neuromuscul Disord. 2015 Jul;25(7):554-62
pubmed: 25913211
Hum Mol Genet. 2011 May 1;20(9):1776-86
pubmed: 21317158
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18259-64
pubmed: 17984063
J Neurol Neurosurg Psychiatry. 1994 Oct;57(10):1274-5
pubmed: 7931399
Acta Neuropathol. 2013 Jul;126(1):109-21
pubmed: 23644820
Neuron. 2016 Jul 6;91(1):56-66
pubmed: 27292537
Muscle Nerve. 2009 Jul;40(1):126-9
pubmed: 19533663
Rehabil Res Pract. 2014;2014:873872
pubmed: 24876969
Brain. 2012 Sep;135(Pt 9):2838-48
pubmed: 22773541
Neuron. 2004 Mar 4;41(5):687-99
pubmed: 15003169
Neurology. 2018 Feb 6;90(6):e518-e524
pubmed: 29321234
Neurobiol Dis. 2009 Apr;34(1):113-20
pubmed: 19211034
Neurology. 1968 Jul;18(7):671-80
pubmed: 4233749
Neuron. 2014 Apr 16;82(2):295-307
pubmed: 24742458
Neurology. 2014 Jun 10;82(23):2077-84
pubmed: 24814851