Balatoni Balázs, Storch Maria K, Swoboda Eva-M, Schönborn Vinzenz, Koziel Agnieszka, Lambrou George N, Hiestand Peter C, Weissert Robert, Foster Carolyn A
Novartis Institutes for BioMedical Research, Brunner Strasse 59, A-1235, Vienna, Austria.
Brain Res Bull. 2007 Oct 19;74(5):307-16. doi: 10.1016/j.brainresbull.2007.06.023. Epub 2007 Jul 30.
FTY720 (fingolimod) is an oral sphingosine 1-phosphate (S1P) receptor modulator under development for the treatment of multiple sclerosis (MS). To elucidate its effects in the central nervous system (CNS), we compared functional parameters of nerve conductance in the DA rat model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) after preventive and therapeutic treatment. We demonstrate that prophylactic therapy protected against the emergence of EAE symptoms, neuropathology, and disturbances to visual and somatosensory evoked potentials (VEP, SEP). Moreover, therapeutic treatment from day 25 to 45 markedly reversed paralysis in established EAE and normalized the electrophysiological responses, correlating with decreased demyelination in the brain and spinal cord. The effectiveness of FTY720 in this model is likely due to several contributing factors. Evidence thus far supports its role in the reduction of inflammation and preservation of blood-brain-barrier integrity. FTY720 may also act via S1P receptors in glial cells to promote endogenous repair mechanisms that complement its immunomodulatory action.
FTY720（芬戈莫德）是一种口服的1-磷酸鞘氨醇（S1P）受体调节剂，正处于研发阶段，用于治疗多发性硬化症（MS）。为了阐明其在中枢神经系统（CNS）中的作用，我们比较了在髓鞘少突胶质细胞糖蛋白（MOG）诱导的实验性自身免疫性脑脊髓炎（EAE）的DA大鼠模型中，预防性和治疗性治疗后神经传导的功能参数。我们证明，预防性治疗可预防EAE症状、神经病理学以及视觉和体感诱发电位（VEP、SEP）的紊乱。此外，从第25天到第45天的治疗性治疗显著逆转了已建立的EAE中的麻痹，并使电生理反应正常化，这与脑和脊髓中脱髓鞘减少相关。FTY720在该模型中的有效性可能归因于几个因素。迄今为止的证据支持其在减轻炎症和维持血脑屏障完整性方面的作用。FTY720也可能通过胶质细胞中的S1P受体起作用，以促进内源性修复机制，补充其免疫调节作用。
