Pivotal cytokines and their transcription factors are the targets of guluronic acid (G2013) for inhibiting the immunopathogenesis process of multiple sclerosis

Drug Dev Res. 2020 Jun;81(4):511-516. doi: 10.1002/ddr.21645. Epub 2020 Feb 26.

Abstract

The α-L-guluronic acid (G2013), is a novel immunosuppressive drug (PCT/EP2017/067920). One of the most popular ideas in designing drugs for multiple sclerosis (MS) is to restrict the main inflammation-related lymphocytes and cytokines. The foremost problems with conventional drugs are their side effects and low efficacy. In order to rectify these problems, we examined the effect of two doses of G2013 on the gene expression of IFN-γ, IL-17, IL-22, T-bet, RORC, and AHR, in MS patients PBMCs. RNA was extracted from peripheral blood mononuclear cell (PBMC) of 12 relapsing-remitting MS patients and 12 healthy volunteers and the effect of two doses of G2013 on the gene expression of IFN-γ, IL-17, IL-22, T-bet, RORC, and AHR, were assessed by real-time PCR. Overall, the results show that G2013 is able to significantly reduce the gene expression of IL-22, AHR, RORC, and T-bet. Collectively, G2013 might be considered and studied as a new drug of possible use to MS patients due to its immunosuppressive property on some of the main inflammatory cytokine and transcription factors.

Keywords: AHR; G2013; Guluronic acid; IL-22; RORC; T-bet; immunosuppressive drugs; multiple sclerosis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Case-Control Studies
  • Cytokines / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation / drug effects
  • Hexuronic Acids / administration & dosage
  • Hexuronic Acids / pharmacology*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / physiopathology
  • Transcription Factors / genetics
  • Young Adult

Substances

  • Cytokines
  • Hexuronic Acids
  • Immunosuppressive Agents
  • Transcription Factors
  • guluronic acid