Abstract
Objective 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.
Methods 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.
Results 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.
Conclusions 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.
Glossary
- ALS=
- amyotrophic lateral sclerosis;
- ALSFRS=
- Amyotrophic Lateral Sclerosis Functional Rating Scale;
- AMAT=
- Adult Myopathy Assessment Tool;
- AR=
- androgen receptor;
- CK=
- creatine kinase;
- KD=
- Kennedy disease;
- LMN=
- lower motor neuron;
- NfL=
- neurofilament light chain;
- PRL=
- progression rate to last visit;
- SBG=
- streptavidin-β-galactosidase;
- SBMA=
- spinal and bulbar muscular atrophy;
- SBMAFRS=
- Spinal and Bulbar Muscular Atrophy Functional Rating Scale
Footnotes
↵* These authors contributed equally to this work.
↵‡ These authors contributed equally to this work.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing Charge was funded by Medical Research Council UK.
CME Course: NPub.org/cmelist
- Received August 12, 2018.
- Accepted in final form November 5, 2018.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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