Background: Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis
(RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient
and motivating results of international Phase III clinical trial of β-D-Mannuronic acid (M2000) patented
EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was
Objectives: This study aimed to assess the oral administration effects of this new drug on gene expression
of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and
CCL2/MCP-1 in PBMCs of patients with active form of RA.
Methods: Twelve patients suffering from RA, with inadequate response to conventional drugs were
selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated
to them for 12 weeks. The mRNA expression of target molecules was then evaluated in
PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared
to healthy controls. Patents related to this study were also reviewed.
Results: The results showed that M2000 was able to significantly down-regulate the mRNA expression
of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene
expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments
in the patients.
Conclusion: Taken together, the results of this investigation revealed the part of molecular and immunological
mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine
ligands and receptors mediated processes.