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 identi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Human Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnhum.2018.00226/full |
| _version_ | 1818504350207574016 |
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| author | Daniel Stoessel Daniel Stoessel Daniel Stoessel Jan-Patrick Stellmann Jan-Patrick Stellmann Anne Willing Birte Behrens Sina C. Rosenkranz Sina C. Rosenkranz Sibylle C. Hodecker Sibylle C. Hodecker Klarissa H. Stürner Klarissa H. Stürner Stefanie Reinhardt Sabine Fleischer Christian Deuschle Walter Maetzler Walter Maetzler Daniela Berg Daniela Berg Christoph Heesen Christoph Heesen Dirk Walther Dirk Walther Nicolas Schauer Manuel A. Friese Ole Pless |
| author_facet | Daniel Stoessel Daniel Stoessel Daniel Stoessel Jan-Patrick Stellmann Jan-Patrick Stellmann Anne Willing Birte Behrens Sina C. Rosenkranz Sina C. Rosenkranz Sibylle C. Hodecker Sibylle C. Hodecker Klarissa H. Stürner Klarissa H. Stürner Stefanie Reinhardt Sabine Fleischer Christian Deuschle Walter Maetzler Walter Maetzler Daniela Berg Daniela Berg Christoph Heesen Christoph Heesen Dirk Walther Dirk Walther Nicolas Schauer Manuel A. Friese Ole Pless |
| author_sort | Daniel Stoessel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T21:35:59Z |
| format | Article |
| id | doaj.art-6e3fe203b67340c084d0541f37c9575e |
| institution | Directory Open Access Journal |
| issn | 1662-5161 |
| language | English |
| last_indexed | 2024-12-10T21:35:59Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Human Neuroscience |
| spelling | doaj.art-6e3fe203b67340c084d0541f37c9575e2022-12-22T01:32:39ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612018-06-011210.3389/fnhum.2018.00226378428Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course MonitoringDaniel Stoessel0Daniel Stoessel1Daniel Stoessel2Jan-Patrick Stellmann3Jan-Patrick Stellmann4Anne Willing5Birte Behrens6Sina C. Rosenkranz7Sina C. Rosenkranz8Sibylle C. Hodecker9Sibylle C. Hodecker10Klarissa H. Stürner11Klarissa H. Stürner12Stefanie Reinhardt13Sabine Fleischer14Christian Deuschle15Walter Maetzler16Walter Maetzler17Daniela Berg18Daniela Berg19Christoph Heesen20Christoph Heesen21Dirk Walther22Dirk Walther23Nicolas Schauer24Manuel A. Friese25Ole Pless26Metabolomic Discoveries GmbH, Potsdam, GermanyInstitut für Biochemie und Biologie, Universität Potsdam, Potsdam, GermanyBioinformatik, Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyKlinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyNeurodegenerative Erkrankungen, Hertie-Institut für klinische Hirnforschung, Eberhardt-Karls-Universität Tübingen, Tübingen, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyKlinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyKlinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyKlinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyNeurodegenerative Erkrankungen, Hertie-Institut für klinische Hirnforschung, Eberhardt-Karls-Universität Tübingen, Tübingen, GermanyNeurodegenerative Erkrankungen, Hertie-Institut für klinische Hirnforschung, Eberhardt-Karls-Universität Tübingen, Tübingen, GermanyDepartment of Neurology, Christian-Albrechts-Universität zu Kiel, Kiel, GermanyNeurodegenerative Erkrankungen, Hertie-Institut für klinische Hirnforschung, Eberhardt-Karls-Universität Tübingen, Tübingen, GermanyDepartment of Neurology, Christian-Albrechts-Universität zu Kiel, Kiel, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyKlinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyInstitut für Biochemie und Biologie, Universität Potsdam, Potsdam, GermanyBioinformatik, Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, GermanyMetabolomic Discoveries GmbH, Potsdam, GermanyZentrum für Molekulare Neurobiologie Hamburg, Institut für Neuroimmunologie und Multiple Sklerose, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyFraunhofer IME ScreeningPort, Hamburg, GermanyPrimary 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.https://www.frontiersin.org/article/10.3389/fnhum.2018.00226/fulluntargeted metabolomicsbiomarkerPPMSMS neurodegenerationLysoPC(20:0) |
| spellingShingle | Daniel Stoessel Daniel Stoessel Daniel Stoessel Jan-Patrick Stellmann Jan-Patrick Stellmann Anne Willing Birte Behrens Sina C. Rosenkranz Sina C. Rosenkranz Sibylle C. Hodecker Sibylle C. Hodecker Klarissa H. Stürner Klarissa H. Stürner Stefanie Reinhardt Sabine Fleischer Christian Deuschle Walter Maetzler Walter Maetzler Daniela Berg Daniela Berg Christoph Heesen Christoph Heesen Dirk Walther Dirk Walther Nicolas Schauer Manuel A. Friese Ole Pless Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring Frontiers in Human Neuroscience untargeted metabolomics biomarker PPMS MS neurodegeneration LysoPC(20:0) |
| title | Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring |
| title_full | Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring |
| title_fullStr | Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring |
| title_full_unstemmed | Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring |
| title_short | Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring |
| title_sort | metabolomic profiles for primary progressive multiple sclerosis stratification and disease course monitoring |
| topic | untargeted metabolomics biomarker PPMS MS neurodegeneration LysoPC(20:0) |
| url | https://www.frontiersin.org/article/10.3389/fnhum.2018.00226/full |
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