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

• DOI: 10.1073/pnas.2123265119
• Publication Date: 2022-06-14T19:21:17Z
• Authors: 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
• Keywords: Metabolic pathway; Sphingolipid

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 (RRMS) 14 healthy age-matched controls. Of 632 known detected, 60 were significantly altered in RRMS. Bioinformatics analysis identified an metabotype RRMS, represented by four changed metabolic pathways glycerophospholipid, citrate cycle, sphingolipid, pyruvate metabolism. Interestingly, common upstream pathway feeding these is glycolysis pathway. Real-time bioenergetic patient-derived peripheral blood mononuclear cells showed enhanced glycolysis, supporting state immune cells. Experimental autoimmune encephalomyelitis mice treated glycolytic inhibitor 2-deoxy-D-glucose ameliorated disease progression inhibited pathology promoting antiinflammatory phenotype monocytes/macrophage central nervous system. Our study provided a proof principle how blood-based metabolomic approach using patient samples could lead to identification therapeutic target developing potential therapy.