Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Germany.
Mult Scler. 2012 Mar;18(3):258-63. doi: 10.1177/1352458512438723.
FTY720 (fingolimod; Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator, is the first oral disease-modifying therapy to be approved for the treatment of relapsing-remitting multiple sclerosis. FTY720 is rapidly converted in vivo to the active S-fingolimod-phosphate, which binds to S1P receptors. This action inhibits egress of lymphocytes from the lymph nodes, preventing entry into the blood and thus infiltration into the central nervous system. More recent studies, however, convincingly show that FTY720 crosses the blood-brain barrier, where it is thought to act on S1P receptors on cells within the central nervous system, such as astrocytes, oligodendrocytes or microglia. Here we discuss the evidence showing that FTY720 also plays a role in remyelination and repair within the brain. While the mechanisms of action still require firm elucidation, it is clear that FTY720 could also be reparative, extending its therapeutic potential for multiple sclerosis.
FTY720（fingolimod；Gilenya®）是一种鞘氨醇 1-磷酸（S1P）受体调节剂，是首个被批准用于治疗复发缓解型多发性硬化症的口服疾病修正治疗药物。FTY720 在体内迅速转化为活性 S- fingolimod-磷酸，与 S1P 受体结合。该作用抑制淋巴细胞从淋巴结迁出，防止进入血液，从而阻止其渗透进入中枢神经系统。然而，最近的研究令人信服地表明，FTY720 可穿过血脑屏障，在中枢神经系统内的细胞（如星形胶质细胞、少突胶质细胞或小胶质细胞）上发挥作用。在此，我们讨论了表明 FTY720 还在大脑内的髓鞘修复和修复中发挥作用的证据。虽然作用机制仍需要明确阐明，但 FTY720 也可能具有修复作用，从而扩展其在多发性硬化症中的治疗潜力。
