Metabolomic profiles for primary progressive multiple sclerosis stratification and disease course monitoring

  • Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the relapsing remitting subtype (RRMS), primary neurodegenerative disease (Parkinson’s disease, PD), and healthy controls (HCs) and that significantly change during the disease course and could serve as surrogate markers of multiple sclerosis (MS)-associated neurodegeneration over time. We applied untargeted high-resolution metabolomics to plasma samples to identify PPMS-specific signatures, validated our findings in independent sex- and age-matched PPMS and HC cohorts and built discriminatory models by partial least square discriminant analysis (PLS-DA). This signature was compared to sex- and age-matched RRMS patients, to patients with PD and HC.Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the relapsing remitting subtype (RRMS), primary neurodegenerative disease (Parkinson’s disease, PD), and healthy controls (HCs) and that significantly change during the disease course and could serve as surrogate markers of multiple sclerosis (MS)-associated neurodegeneration over time. We applied untargeted high-resolution metabolomics to plasma samples to identify PPMS-specific signatures, validated our findings in independent sex- and age-matched PPMS and HC cohorts and built discriminatory models by partial least square discriminant analysis (PLS-DA). This signature was compared to sex- and age-matched RRMS patients, to patients with PD and HC. Finally, we investigated these metabolites in a longitudinal cohort of PPMS patients over a 24-month period. PLS-DA yielded predictive models for classification along with a set of 20 PPMS-specific informative metabolite markers. These metabolites suggest disease-specific alterations in glycerophospholipid and linoleic acid pathways. Notably, the glycerophospholipid LysoPC(20:0) significantly decreased during the observation period. These findings show potential for diagnosis and disease course monitoring, and might serve as biomarkers to assess treatment efficacy in future clinical trials for neuroprotective MS therapies.show moreshow less

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Author:Daniel StoesselORCiDGND, Jan-Patrick Stellmann, Anne Willing, Birte Behrens, Sina C. Rosenkranz, Sibylle C. Hodecker, Klarissa H. Stürner, Stefanie Reinhardt, Sabine Fleischer, Christian Deuschle, Walter Maetzler, Daniela Berg, Christoph Heesen, Dirk WaltherORCiDGND, Nicolas Schauer, Manuel A. Friese, Ole PlessORCiD
URN:urn:nbn:de:kobv:517-opus4-426307
DOI:https://doi.org/10.25932/publishup-42630
ISSN:1866-8372
Parent Title (English):Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe
Series (Serial Number):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (694)
Document Type:Postprint
Language:English
Date of first Publication:2019/04/05
Year of Completion:2018
Publishing Institution:Universität Potsdam
Release Date:2019/04/05
Tag:LysoPC(20:0); MS neurodegeneration; PPMS; biomarker; untargeted metabolomics
Issue:694
Pagenumber:13
Source:Frontiers in Human Neuroscience 12 (2018) Art. 226 DOI: 10.3389/fnhum.2018.00226
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Peer Review:Referiert
Publication Way:Open Access
Grantor:Frontiers
Licence (German):License LogoCreative Commons - Namensnennung, 4.0 International