Blood-based untargeted metabolomics in relapsing-remitting multiple sclerosis revealed the testable therapeutic target

Insha Zahoor; Hamid Suhail; Indrani Datta; Mohammad Ejaz Ahmed; Laila M Poisson; Jeffrey Waters; Faraz Rashid; Rui Bin; Jaspreet Singh; Mirela Cerghet; Ashok Kumar; Md Nasrul Hoda; Ramandeep Rattan; Ashutosh K Mangalam; Shailendra Giri

doi:10.1073/pnas.2123265119

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Blood-based untargeted metabolomics in relapsing-remitting multiple sclerosis revealed the testable therapeutic target

Journal article

Open access

Peer reviewed

Blood-based untargeted metabolomics in relapsing-remitting multiple sclerosis revealed the testable therapeutic target

Insha Zahoor, Hamid Suhail, Indrani Datta, Mohammad Ejaz Ahmed, Laila M Poisson, Jeffrey Waters, Faraz Rashid, Rui Bin, Jaspreet Singh, Mirela Cerghet, …

Proceedings of the National Academy of Sciences - PNAS, Vol.119(25), pp.e2123265119-e2123265119

06/21/2022

DOI: 10.1073/pnas.2123265119

PMCID: PMC9231486

PMID: 35700359

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Abstract

Metabolic aberrations impact the pathogenesis of multiple sclerosis (MS) and possibly can provide clues for new treatment strategies. Using untargeted metabolomics, we measured serum metabolites from 35 patients with relapsing-remitting multiple sclerosis (RRMS) and 14 healthy age-matched controls. Of 632 known metabolites detected, 60 were significantly altered in RRMS. Bioinformatics analysis identified an altered metabotype in patients with RRMS, represented by four changed metabolic pathways of glycerophospholipid, citrate cycle, sphingolipid, and pyruvate metabolism. Interestingly, the common upstream metabolic pathway feeding these four pathways is the glycolysis pathway. Real-time bioenergetic analysis of the patient-derived peripheral blood mononuclear cells showed enhanced glycolysis, supporting the altered metabolic state of immune cells. Experimental autoimmune encephalomyelitis mice treated with the glycolytic inhibitor 2-deoxy-D-glucose ameliorated the disease progression and inhibited the disease pathology significantly by promoting the antiinflammatory phenotype of monocytes/macrophage in the central nervous system. Our study provided a proof of principle for how a blood-based metabolomic approach using patient samples could lead to the identification of a therapeutic target for developing potential therapy.

Multiple Sclerosis

Animals

Encephalomyelitis, Autoimmune, Experimental - metabolism

Humans

Leukocytes, Mononuclear - metabolism

Metabolomics

Mice

Multiple Sclerosis, Relapsing-Remitting

Details

Title: Subtitle: Blood-based untargeted metabolomics in relapsing-remitting multiple sclerosis revealed the testable therapeutic target
Creators: Insha Zahoor - Henry Ford Health System
Hamid Suhail - Henry Ford Health System
Indrani Datta - Henry Ford Health System
Mohammad Ejaz Ahmed - Henry Ford Health System
Laila M Poisson - Henry Ford Health System
Jeffrey Waters - Henry Ford Health System
Faraz Rashid - Henry Ford Health System
Rui Bin - Henry Ford Health System
Jaspreet Singh - Henry Ford Health System
Mirela Cerghet - Henry Ford Health System
Ashok Kumar - Wayne State University
Md Nasrul Hoda - Henry Ford Health System
Ramandeep Rattan - Henry Ford Health System
Ashutosh K Mangalam - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 5224
Shailendra Giri - Henry Ford Health System
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.119(25), pp.e2123265119-e2123265119
DOI: 10.1073/pnas.2123265119
PMID: 35700359
PMCID: PMC9231486
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Grant note: NS112727 / HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) AI144004 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) RG-1807-31964 / National Multiple Sclerosis Society Michigan Chapter (MS) RG-1508-05912 / National Multiple Sclerosis Society Michigan Chapter (MS)
Language: English
Date published: 06/21/2022
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984267658002771

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