7月29日，《免疫学期刊》（Journal of Immunology）在线发表了同济大学生命科学与技术学院-中科院上海药物所合作研究的有关老药新用的最新成果。

多发性硬化症（MS）是一类影响中枢神经系统的自身免疫性疾病，是造成青壮年人瘫痪的最重要原因之一。在中科院上海药物研究所谢欣研究员的指导下，同济大学博士生王烈峰、副教授杜昌升等在研究G蛋白偶联受体（GPCR）与该疾病关系时发现，有一类GPCR（半胱氨酸白三烯受体1，CysLT1）在MS的动物模型EAE小鼠上随疾病进程表达显著提高。CysLT1是一个已知的药物作用靶点，其拮抗剂孟鲁司特、扎鲁司特等都是用于抗哮喘的药物，且孟鲁司特是全球销售最好的前二十个药物之一。但该受体及药物在MS中的作用从未有人报道。

研究发现，孟鲁司特、扎鲁司特可以有效缓解EAE动物的临床症状，减轻自身免疫性T细胞对中枢神经系统的浸润。机制研究发现，CysLT1拮抗剂孟鲁司特可以阻止T细胞的趋化，保护血脑屏障的完整性，从而缓解EAE的发病。该研究不仅发现了可以有效治疗MS的药物作用靶点CysLT1受体，也提示许多抗哮喘的老药有可能用于自身免疫性疾病的治疗。

谢欣是中科院上海药物所课题组长，国家新药筛选中心模型建立II部主管，同济大学生命科学与技术学院兼职教授，博士生导师。主要从事基于GPCR的新药发现及机制研究，以及小分子化合物调控干细胞命运的研究。其小组刚发表文章揭示抗抑郁/躁狂的老药LiCl能显著提高诱导多能干细胞（iPS）的诱导效率（Cell Research, 2011）。

本研究工作得到自然科学基金委、科技部以及上海市科委项目的支持。

英文论文摘要：

Antiasthmatic Drugs Targeting the Cysteinyl Leukotriene Receptor 1 Alleviate Central Nervous System Inflammatory Cell Infiltration and Pathogenesis of Experimental Autoimmune Encephalomyelitis

Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and are considered to play a key role in inflammatory diseases such as asthma. Antagonists targeting the receptor of CysLTs (CysLT1) are currently used as antiasthmatic drugs. CysLTs have also been implicated in other inflammatory reactions. In this study, we report that in experimental autoimmune encephalomyelitis animals, CysLT1 is upregulated in immune tissue and the spinal cord, and CysLT levels in the blood and cerebrospinal fluid are also higher than in normal mice. Two clinically used antiasthma drugs, montelukast and zafirlukast, both targeting CysLT1, effectively block the CNS infiltration of inflammatory cells and thus reduce the incidence, peak severity, and cumulative clinical scores. Further study indicated that CysLT1 signaling does not affect the differentiation of pathogenic T helper cells. It might affect the pathogenesis of experimental autoimmune encephalomyelitis by increasing the secretion of IL-17 from myelin oligodendrocyte glycoprotein-specific T cells, increasing the permeability of the blood–brain barrier and inducing chemotaxis of T cells. These effects can be blocked by CysLT1 antagonists. Our findings indicate that the antiasthmatic drugs against CysLT1 can also be used to treat multiple sclerosis.