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Evaluation of the Effect of Mannuronic Acid As a Novel Nsaid With Immunosuppressive Properties on Expression of Socs1, Socs3, Ship1, and Traf6 Genes and Serum Levels of Il-6 and Tnf-Α in Patients With Multiple Sclerosis Publisher Pubmed



Najafi S1 ; Saadat P2 ; Beladi Moghadam N3 ; Manoucherinia A4 ; Aghazadeh Z1 ; Vali Mohammadi A5 ; Pashaiefar H6 ; Hosseini M7 ; Mirshafiey A1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  3. 3. Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
  4. 4. Department of Clinical Neuroscience (CNS), Karolinska Institutet, Stockholm, Sweden
  5. 5. Islamic Azad University, Shiraz, Iran
  6. 6. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Clinical Pharmacology Published:2021


Abstract

Multiple sclerosis (MS) is described as a chronic inflammatory, demyelinating disease of the central nervous system on an autoimmune basis, which is the most frequent reason for nontraumatic disability in youth. The efficacy and safety of β-D-nannuronic acid (M2000) as a novel immunosuppressive drug (patented PCT/EP2017/067920) has been shown in an experimental model of MS and also in a phase 2 clinical trial. The effects of M2000 on SOCS1, SOCS3, TRAF6, and SHIP1 gene expression and also serum levels of IL-6 and TNF-α in secondary progressive multiple sclerosis patients have been assessed in this study. In this study, 14 secondary progressive multiple sclerosis patients and 14 healthy subjects (as the control group) were recruited from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). Gene expression of SOCS1, SOCS3, TRAF6, and SHIP1 was measured at baseline and after 6 months of therapy with M2000 using a quantitative real-time polymerase chain reaction method. Furthermore, the serum levels of IL-6 and TNF-α were assessed by the enzyme-linked immunosorbent assay method. Our results showed that the gene expression of SOCS1, SOCS3, and SHIP1 was increased after 6 months of therapy with M2000 in MS patients. Moreover, the serum levels of IL-6 and TNF-α of patients declined compared with baseline, but this was not statistically significant. The results of this study demonstrated that M2000, with immunosuppressive properties, could upregulate SOCS1, SOCS3, and SHIP1 genes in patients with secondary progressive multiple sclerosis. © 2021, The American College of Clinical Pharmacology
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