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      Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by 1H-NMR Spectroscopy

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          Abstract

          Metabolomic research has emerged as a promising approach to identify potential biomarkers in multiple sclerosis (MS). The aim of the present study was to determine the effect of interferon beta (IFN ß) on the metabolome of MS patients to explore possible biomarkers of disease activity and therapeutic response. Twenty-one MS patients starting IFN ß therapy (Rebif® 44 μg; s.c. 3 times per week) were enrolled. Blood samples were obtained at baseline and after 6, 12, and 24 months of IFN ß treatment and were analyzed by high-resolution nuclear magnetic resonance spectroscopy. Changes in metabolites were analyzed. After IFN ß exposure, patients  were divided into responders and nonresponders according to the “no evidence of disease activity” (NEDA-3) definition (absence of relapses, disability progression, and magnetic resonance imaging activity), and samples obtained at baseline were analyzed to evaluate the presence of metabolic differences predictive of IFN ß response. The results of the investigation demonstrated differential distribution of baseline samples compared to those obtained during IFN ß exposure, particularly after 24 months of treatment ( R 2 X = 0.812, R 2 Y = 0.797, Q 2 = 0.613, p = 0.003). In addition, differences in the baseline metabolome between responder and nonresponder patients with respect to lactate, acetone, 3-OH-butyrate, tryptophan, citrate, lysine, and glucose levels were found ( R 2 X = 0.442, R 2 Y = 0.768, Q 2 = 0.532, p = 0.01). In conclusion, a metabolomic approach appears to be a promising, noninvasive tool that could potentially contribute to predicting the efficacy of MS therapies.

          Electronic supplementary material

          The online version of this article (10.1007/s13311-019-00721-8) contains supplementary material, which is available to authorized users.

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          Author and article information

          Contributors
          lorena.lorefice@hotmail.it
          Journal
          Neurotherapeutics
          Neurotherapeutics
          Neurotherapeutics
          Springer International Publishing (Cham )
          1933-7213
          1878-7479
          28 February 2019
          July 2019
          : 16
          : 3
          : 797-807
          Affiliations
          [1 ] ISNI 0000 0004 1755 3242, GRID grid.7763.5, Multiple Sclerosis Centre, Department of Medical Sciences and Public Health, Binaghi Hospital, , University of Cagliari, ; via Is Guadazzonis 2, 09126 Cagliari, Italy
          [2 ] ISNI 0000 0004 1758 4006, GRID grid.476476.0, Merck Serono S.p.A., ; 00176 Rome, Italy
          [3 ] ISNI 0000 0004 1755 3242, GRID grid.7763.5, Department of Biomedical Sciences, , University of Cagliari, ; 09126 Cagliari, Italy
          Article
          PMC6694336 PMC6694336 6694336 721
          10.1007/s13311-019-00721-8
          6694336
          30820880
          f9b3cb6f-a986-4355-9b7e-58cdf72d1878
          © The American Society for Experimental NeuroTherapeutics, Inc. 2019
          History
          Funding
          Funded by: Founded by Merk Serono
          Award ID: NA
          Award Recipient :
          Categories
          Original Article
          Custom metadata
          © The American Society for Experimental NeuroTherapeutics, Inc. 2019

          biomarkers,metabolomic analysis,treatment monitoring,interferon beta 1a,Multiple sclerosis

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