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Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease, and only modest disease-modifying strategies have been established to date. Numerous clinical trials have been conducted in the past years, but have been severely hampered by the wide-ranging heterogeneity o...

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Autores principales: Dreger, Marie, Steinbach, Robert, Otto, Markus, Turner, Martin R, Grosskreutz, Julian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921583/
https://www.ncbi.nlm.nih.gov/pubmed/35105727
http://dx.doi.org/10.1136/jnnp-2021-327503
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author Dreger, Marie
Steinbach, Robert
Otto, Markus
Turner, Martin R
Grosskreutz, Julian
author_facet Dreger, Marie
Steinbach, Robert
Otto, Markus
Turner, Martin R
Grosskreutz, Julian
author_sort Dreger, Marie
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease, and only modest disease-modifying strategies have been established to date. Numerous clinical trials have been conducted in the past years, but have been severely hampered by the wide-ranging heterogeneity of both the biological origins and clinical characteristics of the disease. Thus, reliable biomarkers of disease activity are urgently needed to stratify patients into homogenous groups with aligned disease trajectories to allow a more effective design of clinical trial. In this review, the most promising candidate biomarkers in the cerebrospinal fluid (CSF) of patients with ALS will be summarised. Correlations between biomarker levels and clinical outcome parameters are discussed, while highlighting potential pitfalls and intercorrelations of these clinical parameters. Several CSF molecules have shown potential as biomarkers of progression and prognosis, but large, international, multicentric and longitudinal studies are crucial for validation. A more standardised choice of clinical endpoints in these studies, as well as the application of individualised models of clinical progression, would allow the quantification of disease trajectories, thereby allowing a more accurate analysis of the clinical implications of candidate biomarkers. Additionally, a comparative analysis of several biomarkers and ideally the application of a multivariate analysis including comprehensive genotypic, phenotypic and clinical characteristics collectively contributing to biomarker levels in the CSF, could promote their verification. Thus, reliable prognostic markers and markers of disease activity may improve clinical trial design and patient management in the direction of precision medicine.
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spelling pubmed-89215832022-03-25 Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis Dreger, Marie Steinbach, Robert Otto, Markus Turner, Martin R Grosskreutz, Julian J Neurol Neurosurg Psychiatry Neuromuscular Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease, and only modest disease-modifying strategies have been established to date. Numerous clinical trials have been conducted in the past years, but have been severely hampered by the wide-ranging heterogeneity of both the biological origins and clinical characteristics of the disease. Thus, reliable biomarkers of disease activity are urgently needed to stratify patients into homogenous groups with aligned disease trajectories to allow a more effective design of clinical trial. In this review, the most promising candidate biomarkers in the cerebrospinal fluid (CSF) of patients with ALS will be summarised. Correlations between biomarker levels and clinical outcome parameters are discussed, while highlighting potential pitfalls and intercorrelations of these clinical parameters. Several CSF molecules have shown potential as biomarkers of progression and prognosis, but large, international, multicentric and longitudinal studies are crucial for validation. A more standardised choice of clinical endpoints in these studies, as well as the application of individualised models of clinical progression, would allow the quantification of disease trajectories, thereby allowing a more accurate analysis of the clinical implications of candidate biomarkers. Additionally, a comparative analysis of several biomarkers and ideally the application of a multivariate analysis including comprehensive genotypic, phenotypic and clinical characteristics collectively contributing to biomarker levels in the CSF, could promote their verification. Thus, reliable prognostic markers and markers of disease activity may improve clinical trial design and patient management in the direction of precision medicine. BMJ Publishing Group 2022-04 2022-02-01 /pmc/articles/PMC8921583/ /pubmed/35105727 http://dx.doi.org/10.1136/jnnp-2021-327503 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Neuromuscular
Dreger, Marie
Steinbach, Robert
Otto, Markus
Turner, Martin R
Grosskreutz, Julian
Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
title Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
title_full Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
title_fullStr Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
title_full_unstemmed Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
title_short Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
title_sort cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
topic Neuromuscular
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921583/
https://www.ncbi.nlm.nih.gov/pubmed/35105727
http://dx.doi.org/10.1136/jnnp-2021-327503
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