Chun Jerold, Brinkmann Volker
Department of Molecular Biology and Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037, USA.
Discov Med. 2011 Sep;12(64):213-28.
Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Until recently, major therapeutic treatments have relied on agents requiring injection delivery. In September 2010, fingolimod/FTY720 (Gilenya, Novartis) was approved by the FDA as the first oral treatment for relapsing forms of MS. Fingolimod is a novel compound produced by chemical modification of a fungal precursor. Its active metabolite, formed by in vivo phosphorylation, modulates sphingosine 1-phosphate (S1P) receptors that are a subset of a larger family of cell-surface, G protein-coupled receptors (GPCRs) mediating the effects of bioactive lipids known as lysophospholipids. Fingolimod's mechanism of action in MS is not completely understood; however, its relevant biology indicates a fundamentally different mechanism compared to all previously approved MS therapies, with evolving research supporting both immunological and nervous system activities. This duality may herald a paradigm shift in the treatment of MS and other neurological disorders.
多发性硬化症（MS）是一种慢性自身免疫性疾病，通过脱髓鞘和神经退行性变影响中枢神经系统（CNS）。直到最近，主要的治疗方法都依赖于需要注射给药的药物。2010年9月，芬戈莫德/FTY720（捷灵亚，诺华公司）被美国食品药品监督管理局（FDA）批准为复发型MS的首个口服治疗药物。芬戈莫德是一种通过对真菌前体进行化学修饰而产生的新型化合物。其活性代谢产物由体内磷酸化形成，可调节1-磷酸鞘氨醇（S1P）受体，该受体是细胞表面更大的G蛋白偶联受体（GPCR）家族的一个子集，介导被称为溶血磷脂的生物活性脂质的作用。芬戈莫德在MS中的作用机制尚未完全明确；然而，其相关生物学特性表明，与所有先前批准的MS治疗方法相比，其作用机制存在根本差异，不断发展的研究支持其在免疫和神经系统方面的活性。这种双重性可能预示着MS和其他神经系统疾病治疗模式的转变。
