The Effects of Mannuronic Acid on IL-1β, IL-17A, STAT1, and STAT3 Gene Expressions and TLR2 and TLR4 Molecules in Multiple Sclerosis

• Published in: Journal of clinical pharmacology Vol. 62; no. 6; p. 762
• Main Authors: Najafi, Soheil, Saadat, Payam, Beladi Moghadam, Nahid, Manoucherinia, Ali, Aghazadeh, Zahra, Vali Mohammadi, Anita, Noorbakhsh, Seyyedeh Masoomeh, Movahedi, Monireh, Nikouei Moghaddam, Mohammad Reza, Pashaiefar, Hossein, Mirshafiey, Abbas
• Format: Journal Article
• Language: English
• Published: England 01.06.2022
• Subjects: Clinical Trials, Phase II as Topic; Gene Expression; Hexuronic Acids; Humans; Interleukin-17 - genetics; Leukocytes, Mononuclear - metabolism; Multiple Sclerosis - drug therapy; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; STAT1 Transcription Factor - pharmacology; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; TLR; IL-17A; STAT1; multiple sclerosis; mannuronic acid; STAT3
• ISSN: 1552-4604
• DOI: 10.1002/jcph.2008

Multiple sclerosis (MS) is a chronic neurologic disease defined by inflammation and demyelination of the central nervous system that comes with variable degrees of axonal and neuronal damage. The efficacy of β-D-mannuronic acid (M2000) as a novel drug with immunosuppressive properties (patented: PCT/EP2017/067920), has been shown in an experimental model of MS. In this study, the effects of M2000 on interleukin (IL)-1β, IL-17A, signal transducer and activator of transcription (STAT) 1, and STAT3 gene expressions and Toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) molecules in patients with secondary progressive MS were evaluated. In this study, 14 patients with secondary progressive MS and 14 healthy subjects (as control group) were entered from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). The gene expressions of IL-1β, IL-17A, STAT1, and STAT3 were assessed at the baseline and then measured after 6 months of therapy with M2000 by using the quantitative real-time polymerase chain reaction method. Moreover, the expressions of TLR2 and TLR4 molecules on peripheral blood mononuclear cells were evaluated by the flow cytometry method. The gene expressions of IL-17A, STAT1, and STAT3 in patients with MS decreased after 6 months of therapy with M2000 comparing before treatment. Also, the gene expression of IL-1β decreased numerically after 6 months. Furthermore, the expressions of TLR2 and TLR4 on PBMCs of the patients declined when compared to baseline. The results of this investigation revealed that M2000 could downregulate IL-17, STAT1, and STAT3 genes in patients with secondary progressive MS and also reduce the expressions of TLR2 and TLR4 on PBMCs. Moreover, M2000 declined numerically IL-β gene expression.