Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Curr Drug Discov Technol. 2020;17(5):704-710. doi: 10.2174/1570163816666190620113320.
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.
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.
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.
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.
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.
类风湿关节炎（RA）是一种复杂的疾病，涉及到数量未知的基因，并影响到全身大量的器官、组织和部位。它影响着全球约 1%的人口。β-D-甘露糖醛酸（M2000）作为一种具有免疫抑制特性的新型 NSAID，已在体外、体内检查和临床试验中得到证实，其安全性和治疗效果在强直性脊柱炎（AS）患者中进行了 1/11 期试验，在类风湿关节炎（RA）患者中进行了 1/11 期和 111 期试验。
在这项研究中，我们的目标是评估口服 M2000 对基质金属蛋白酶（MMP2、MMP9）和金属蛋白酶组织抑制剂（TIMP1、TIMP2）基因表达的治疗效果，这些基因表达作为类风湿关节炎进展中的炎症分子。
该研究纳入了 15 名对常规药物反应不足的 RA 患者。因此，甘露糖酸被用作常规治疗方案的添加剂。该研究是一项单盲研究。M2000 的剂量为每天口服 500mg，每天两次，共 12 周。有 15 名健康参与者被视为对照组。从健康对照组和 RA 患者中各采集一次血样，从 RA 患者中采集两次血样，分别在治疗前和治疗后采集。采用实时 PCR 法检测外周血单个核细胞（PBMCs）中 MMP2、MMP9、TIMP1 和 TIMP2 的基因表达水平。
与治疗前相比，RA 患者接受 M2000 治疗后 MMP2 和 MMP9 的基因表达水平显著降低。另一方面，与治疗前相比，RA 患者接受甘露糖酸治疗后 TIMP2 的基因表达水平显著升高，但与治疗前的 RA 患者组和对照组之间无显著差异。与其他分子相反，与治疗前的 RA 患者相比，TIMP1 水平没有差异。
我们的研究结果表明，β-D-甘露糖醛酸作为一种具有免疫抑制特性的新型 NSAID，对 RA 患者 MMP2、MMP9 和 TIMP2 分子的基因表达水平有显著影响。
