Show simple item record

dc.contributor.authorHuang, Fen
dc.contributor.authorZhu, Yuda
dc.contributor.authorHsiao-Nakamoto, Jennifer
dc.contributor.authorTang, Xinyan
dc.contributor.authorDugas, Jason C.
dc.contributor.authorMoscovitch-Lopatin, Miriam
dc.contributor.authorGlass, Jonathan D.
dc.contributor.authorBrown, Robert H. Jr.
dc.contributor.authorLadha, Shafeeq S.
dc.contributor.authorLacomis, David
dc.contributor.authorHarris, Jeffrey M.
dc.contributor.authorScearce-Levie, Kimberly
dc.contributor.authorHo, Carole
dc.contributor.authorBowser, Robert
dc.contributor.authorBerry, James D.
dc.date2022-08-11T08:09:56.000
dc.date.accessioned2022-08-23T16:49:34Z
dc.date.available2022-08-23T16:49:34Z
dc.date.issued2020-06-09
dc.date.submitted2020-07-01
dc.identifier.citation<p>Huang F, Zhu Y, Hsiao-Nakamoto J, Tang X, Dugas JC, Moscovitch-Lopatin M, Glass JD, Brown RH Jr, Ladha SS, Lacomis D, Harris JM, Scearce-Levie K, Ho C, Bowser R, Berry JD. Longitudinal biomarkers in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2020 Jun 9. doi: 10.1002/acn3.51078. Epub ahead of print. PMID: 32515902. <a href="https://doi.org/10.1002/acn3.51078">Link to article on publisher's site</a></p>
dc.identifier.issn2328-9503 (Linking)
dc.identifier.doi10.1002/acn3.51078
dc.identifier.pmid32515902
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41488
dc.description.abstractOBJECTIVE: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects. METHODS: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from > /=2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations. Additional healthy control CSF samples (n = 35) were obtained from multiple sources. We stratified PALS into fast- and slow-progression subgroups using the ALS Functional Rating Scale-Revised change rate. We compared cytokines/chemokines and neurofilament (NF) levels between PALS and controls, among progression subgroups, and in those with C9orf72 mutations. RESULTS: We found significant elevations of cytokines, including MCP-1, IL-18, and neurofilaments (NFs), indicators of neurodegeneration, in PALS versus controls. Among PALS, these cytokines and NFs were significantly higher in fast-progression and C9orf72 mutation subgroups versus slow progressors. Analyte levels were generally stable over time, a key feature for monitoring treatment effects. We demonstrated that CSF/plasma neurofilament light chain (NFL) levels may predict disease progression, and stratification by NFL levels can enrich for more homogeneous patient groups. INTERPRETATION: Longitudinal stability of cytokines and NFs in PALS support their use for monitoring responses to immunomodulatory and neuroprotective treatments. NFs also have prognostic value for fast-progression patients and may be used to select similar patient subsets in clinical trials.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32515902&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectamyotrophic lateral sclerosis
dc.subjectALS
dc.subjectbiomarkers
dc.subjectcytokines
dc.subjectneurofilaments
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiological Factors
dc.subjectNervous System Diseases
dc.subjectNeurology
dc.subjectNeuroscience and Neurobiology
dc.titleLongitudinal biomarkers in amyotrophic lateral sclerosis
dc.typeJournal Article
dc.source.journaltitleAnnals of clinical and translational neurology
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5293&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4267
dc.identifier.contextkey18332706
refterms.dateFOA2022-08-23T16:49:34Z
html.description.abstract<p>OBJECTIVE: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects.</p> <p>METHODS: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from > /=2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations. Additional healthy control CSF samples (n = 35) were obtained from multiple sources. We stratified PALS into fast- and slow-progression subgroups using the ALS Functional Rating Scale-Revised change rate. We compared cytokines/chemokines and neurofilament (NF) levels between PALS and controls, among progression subgroups, and in those with C9orf72 mutations.</p> <p>RESULTS: We found significant elevations of cytokines, including MCP-1, IL-18, and neurofilaments (NFs), indicators of neurodegeneration, in PALS versus controls. Among PALS, these cytokines and NFs were significantly higher in fast-progression and C9orf72 mutation subgroups versus slow progressors. Analyte levels were generally stable over time, a key feature for monitoring treatment effects. We demonstrated that CSF/plasma neurofilament light chain (NFL) levels may predict disease progression, and stratification by NFL levels can enrich for more homogeneous patient groups.</p> <p>INTERPRETATION: Longitudinal stability of cytokines and NFs in PALS support their use for monitoring responses to immunomodulatory and neuroprotective treatments. NFs also have prognostic value for fast-progression patients and may be used to select similar patient subsets in clinical trials.</p>
dc.identifier.submissionpathoapubs/4267
dc.contributor.departmentDepartment of Neurology


Files in this item

Thumbnail
Name:
acn3.51078.pdf
Size:
622.7Kb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Except where otherwise noted, this item's license is described as © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.