Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Mobility Impairment Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
J Clin Pharmacol. 2021 Oct;61(10):1303-1310. doi: 10.1002/jcph.1879. Epub 2021 Aug 2.
Multiple sclerosis (MS) is described as a chronic inflammatory, demyelinating disease of the central nervous system on an autoimmune basis, which is the most frequent reason for nontraumatic disability in youth. The efficacy and safety of β-D-nannuronic acid (M2000) as a novel immunosuppressive drug (patented PCT/EP2017/067920) has been shown in an experimental model of MS and also in a phase 2 clinical trial. The effects of M2000 on SOCS1, SOCS3, TRAF6, and SHIP1 gene expression and also serum levels of IL-6 and TNF-α in secondary progressive multiple sclerosis patients have been assessed in this study. In this study, 14 secondary progressive multiple sclerosis patients and 14 healthy subjects (as the control group) were recruited from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). Gene expression of SOCS1, SOCS3, TRAF6, and SHIP1 was measured at baseline and after 6 months of therapy with M2000 using a quantitative real-time polymerase chain reaction method. Furthermore, the serum levels of IL-6 and TNF-α were assessed by the enzyme-linked immunosorbent assay method. Our results showed that the gene expression of SOCS1, SOCS3, and SHIP1 was increased after 6 months of therapy with M2000 in MS patients. Moreover, the serum levels of IL-6 and TNF-α of patients declined compared with baseline, but this was not statistically significant. The results of this study demonstrated that M2000, with immunosuppressive properties, could upregulate SOCS1, SOCS3, and SHIP1 genes in patients with secondary progressive multiple sclerosis.
多发性硬化症（MS）被描述为一种中枢神经系统的慢性炎症性脱髓鞘疾病，其基于自身免疫，是青年人非外伤性残疾的最常见原因。β-D-甘露糖醛酸（M2000）作为一种新型免疫抑制剂（专利 PCT/EP2017/067920）在 MS 的实验模型中以及 2 期临床试验中已显示出疗效和安全性。本研究评估了 M2000 对继发进展型多发性硬化症患者 SOCS1、SOCS3、TRAF6 和 SHIP1 基因表达以及血清 IL-6 和 TNF-α 水平的影响。在这项研究中，从 2 期临床试验（临床试验标识符，IRCT2016111313739N6）中招募了 14 名继发进展型多发性硬化症患者和 14 名健康受试者（作为对照组）。使用定量实时聚合酶链反应方法在基线和 M2000 治疗 6 个月后测量 SOCS1、SOCS3、TRAF6 和 SHIP1 的基因表达。此外，通过酶联免疫吸附测定法评估了血清 IL-6 和 TNF-α 水平。我们的结果表明，M2000 治疗 6 个月后 MS 患者 SOCS1、SOCS3 和 SHIP1 的基因表达增加。此外，与基线相比，患者的血清 IL-6 和 TNF-α 水平下降，但这没有统计学意义。这项研究的结果表明，具有免疫抑制特性的 M2000 可以上调继发进展型多发性硬化症患者的 SOCS1、SOCS3 和 SHIP1 基因。
