Aslani Mona, Ahmadzadeh Arman, Rezaieyazdi Zahra, Mortazavi-Jahromi Seyed S, Barati Anis, Hosseini Mostafa, Mirshafiey Abbas
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Recent Pat Inflamm Allergy Drug Discov. 2020;14(1):69-77. doi: 10.2174/1872213X13666191114111822.
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 designed.
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.
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.
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.
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.
类风湿关节炎（RA）患者滑膜中的白细胞浸润大多由趋化因子配体和受体介导。在β-D-甘露糖醛酸（M2000，专利号EP067919，2017）作为一种新型抗炎药物用于RA患者的国际III期临床试验取得有效且鼓舞人心的结果之后，开展了本研究。
本研究旨在评估这种新药口服给药对活动期RA患者外周血单核细胞（PBMCs）中一些趋化因子受体和配体基因表达的影响，这些趋化因子受体和配体包括CXCR4、CXCR3、CCR2、CCR5和CCL2/MCP-1。
选取12例对传统药物反应不佳的RA患者（临床试验标识符IRCT2017100213739N10），给予他们每日1000mg的M2000口服，持续12周。然后使用实时PCR评估患者在接受M2000治疗前后PBMCs中靶分子的mRNA表达，并与健康对照进行比较。还对与本研究相关的专利进行了审查。
结果显示，M2000能够显著下调RA患者PBMCs中CXCR4、CCR2和CCL2/MCP-1的mRNA表达。应当指出的是，靶分子的基因表达情况与患者的临床和临床旁评估结果相协调。
综上所述，本研究结果揭示了基于趋化因子配体和受体介导过程，甘露糖醛酸（M2000）药物在治疗RA中的部分分子和免疫机制。
