Background: Rheumatoid Arthritis (RA) is a complex disease involving an unknown number
of genes, and affecting a large number of organs, tissues, and sites across the body. It is affecting approximately
1% of the population worldwide. The safety and therapeutic efficacy of β-D-mannuronic acid
(M2000) as a novel NSAID with immunosuppressive property has been demonstrated under in vitro, in
vivo examinations and clinical trials phase 1/11 in Ankylosing Spondylitis (AS) patients in addition to
phase I/11 and 111 in Rheumatoid Arthritis (RA) patients.
Objective: In this study, our goal is to evaluate the therapeutic efficacy of oral administration of M2000
on gene expression of the matrix metalloproteinase (MMP2, MMP9) and tissue inhibitor of metalloproteinase
(TIMP1, TIMP2) as inflammatory molecules in the progression of rheumatoid arthritis.
Methods: The study has included 15 RA patients who had an insufficient response to the conventional
drug. Therefore, mannuronic acid was used as an additive to the conventional regime. The research was a
single-blinded study. The dose of M2000 was 500mg orally twice per day for 12 weeks. There were 15
healthy participants considered as control. Blood samples have been collected from both groups once
from the healthy control and twice from RA patients before and after treatment with M2000. The Peripheral
Blood Mononuclear Cells (PBMCs) were isolated for assessment of the gene expression level of
MMP2, MMP9, TIMP1, and TIMP2 using the real-time PCR method.
Results: The gene expression level of MMP2 and MMP9 reported a significant reduction in RA patients
after treatment with M2000 compared to before treatment. On the other hand, the gene expression level
of TIMP2 demonstrated a significant increase in RA patients after treatment with mannuronic acid compared
to before treatment, but there was no significant difference between the group of RA patients before
treatment and the control group. Vice versa to other molecules, there was no significant difference in
the level of TIMP1 in compression with RA patients before and after treatment.
Conclusion: our findings proved that the β -D- mannuronic acid) as a novel NSAID with immunosuppressive
property has a significant effect on the gene expression level of MMP2, MMP9 and TIMP2
molecules in RA patients.