Najafi Soheil, Saadat Payam, Beladi Moghadam Nahid, Manoucherinia Ali, Aghazadeh Zahra, Vali Mohammadi Anita, Noorbakhsh Seyyedeh Masoomeh, Movahedi Monireh, Nikouei Moghaddam Mohammad Reza, Pashaiefar Hossein, Mirshafiey Abbas
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. 2022 Jun;62(6):762-769. doi: 10.1002/jcph.2008. Epub 2022 Jan 7.
Multiple sclerosis (MS) is a chronic neurologic disease defined by inflammation and demyelination of the central nervous system that comes with variable degrees of axonal and neuronal damage. The efficacy of β-D-mannuronic acid (M2000) as a novel drug with immunosuppressive properties (patented: PCT/EP2017/067920), has been shown in an experimental model of MS. In this study, the effects of M2000 on interleukin (IL)-1β, IL-17A, signal transducer and activator of transcription (STAT) 1, and STAT3 gene expressions and Toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) molecules in patients with secondary progressive MS were evaluated. In this study, 14 patients with secondary progressive MS and 14 healthy subjects (as control group) were entered from the phase 2 clinical trial (Clinical Trial identifier, IRCT2016111313739N6). The gene expressions of IL-1β, IL-17A, STAT1, and STAT3 were assessed at the baseline and then measured after 6 months of therapy with M2000 by using the quantitative real-time polymerase chain reaction method. Moreover, the expressions of TLR2 and TLR4 molecules on peripheral blood mononuclear cells were evaluated by the flow cytometry method. The gene expressions of IL-17A, STAT1, and STAT3 in patients with MS decreased after 6 months of therapy with M2000 comparing before treatment. Also, the gene expression of IL-1β decreased numerically after 6 months. Furthermore, the expressions of TLR2 and TLR4 on PBMCs of the patients declined when compared to baseline. The results of this investigation revealed that M2000 could downregulate IL-17, STAT1, and STAT3 genes in patients with secondary progressive MS and also reduce the expressions of TLR2 and TLR4 on PBMCs. Moreover, M2000 declined numerically IL-β gene expression.
多发性硬化症（MS）是一种慢性神经疾病，其特征为中枢神经系统的炎症和脱髓鞘，并伴有不同程度的轴突和神经元损伤。β-D-甘露糖醛酸（M2000）作为一种具有免疫抑制特性的新型药物（专利号：PCT/EP2017/067920），其疗效已在MS实验模型中得到证实。在本研究中，评估了M2000对继发进展型MS患者白细胞介素（IL）-1β、IL-17A、信号转导和转录激活因子（STAT）1和STAT3基因表达以及Toll样受体2（TLR2）和Toll样受体4（TLR4）分子的影响。在本研究中，从2期临床试验（临床试验标识符，IRCT2016111313739N6）纳入了14例继发进展型MS患者和14名健康受试者（作为对照组）。在基线时评估IL-1β、IL-17A、STAT1和STAT3的基因表达，然后在使用M2000治疗6个月后通过定量实时聚合酶链反应法进行测量。此外，通过流式细胞术评估外周血单个核细胞上TLR2和TLR4分子的表达。与治疗前相比，M2000治疗6个月后MS患者中IL-17A、STAT1和STAT3的基因表达下降。此外，6个月后IL-1β的基因表达在数值上有所下降。此外，与基线相比，患者外周血单个核细胞上TLR2和TLR4的表达下降。本研究结果表明，M2000可下调继发进展型MS患者的IL-17、STAT1和STAT3基因，并降低外周血单个核细胞上TLR2和TLR4的表达。此外，M2000在数值上降低了IL-β基因表达。
