Evidence mapPaperPMID 35700359Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

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 and 5 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. A framework for blood biomarker discovery in MS.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
    Review
  5. β-oxidation-mediated differentiation of effector CD4Journal of neuroinflammation · 2026
    Article
  6. Article
  7. Article
  8. Metabolic Programming Drives Protective and Inflammatory Monocyte Fates in Viral Encephalitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  9. Immune-responsive gene 1: The mitochondrial key to Th17 cell pathogenicity in CNS autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Review
  12. Dissecting inflammation in the immunemetabolomic era.Cellular and molecular life sciences : CMLS · 2025
    Review
  13. Article
  14. Article
  15. Drug design, development and therapy · 2025
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Insha ZahoorDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.ORCID 0000-0001-9919-1959
Hamid SuhailDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.
Indrani DattaDepartment of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202.
Mohammad Ejaz AhmedDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.
Laila M PoissonDepartment of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202.
Jeffrey WatersDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.
Faraz RashidDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.
Rui BinDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.
Jaspreet SinghDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.
Mirela CerghetDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.ORCID 0000-0001-8884-6315
Ashok KumarDepartment of Anatomy and Cell Biology, School of Medicine, Wayne State University, Detroit, MI 48202.
Md Nasrul HodaDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.
Ramandeep RattanWomen's Health Services, Henry Ford Health System, Detroit, MI 48202.
Ashutosh K MangalamDepartment of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 5224.ORCID 0000-0002-9926-2531
Shailendra GiriDepartment of Neurology, Henry Ford Health System, Detroit, MI 48202.ORCID 0000-0002-7123-829X
Henry Ford Health System · USUniversity of Iowa · USWayne State University · US

Funding

Pulmonary Toxicology FacilityP30ES005605 · UNIVERSITY OF IOWA · 1990 to 2025
$8.8M
Novel Regulation and Targeting of Macrophages Metabolism in Neuroinflammatory DisordersR01AI144004 · NIAID · HENRY FORD HEALTH SYSTEM · PI SHAILENDRA GIRI · 2022 to 2023
$765k
Targeting NAD metabolism to ameliorate bacterial endophthalmitisR01EY026964 · WAYNE STATE UNIVERSITY · 2025 to 2025
$326k
NEI NIH HHS R01 EY026964NIAID NIH HHS R01 AI144004NIEHS NIH HHS P30 ES005605NINDS NIH HHS R01 NS112727
6 · The paper itself

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.

Indexed as

Drug DevelopmentGlycolysisMetabolomicsMultiple Sclerosis, Relapsing-RemittingAnimalsAnti-Inflammatory AgentsAntimetabolitesDeoxyglucoseEncephalomyelitis, Autoimmune, ExperimentalHumansLeukocytes, MononuclearMiceAnti-Inflammatory AgentsAntimetabolitesDeoxyglucoseEAEglycolysismetabolomicsmultiple sclerosis

Identifiers

PMID35700359
PMCPMC9231486
OpenAlexW2808246037

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.