Oral fingolimod in multiple sclerosis: Therapeutic modulation of the sphingosine-1-phosphate system;Orales Fingolimod bei Multipler Sklerose: Therapeutische Modulation des Sphingosin-1-Phosphat-Systems

Nervenarzt

Volumn 82, Issue 2, 2011, Pages 215-225

  Aktas, O ^a   Ingwersen, J ^a   Kieseier, B ^a   Kury P ^a   Hohlfeld, R ^b,c   Hartung, H P ^a  

^a UNIVERSITY HOSPITAL DÜSSELDORF   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c Institut Max Planck   (Germany)

Author keywords

Fingolimod; Multiple sclerosis; Neural repair mechanism; Sphingosine 1 phosphate system; Therapy

Indexed keywords

BETA1A INTERFERON; FINGOLIMOD; PLACEBO; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE 1 PHOSPHATE RECEPTOR;

ANTIINFLAMMATORY ACTIVITY; ARTICLE; HUMAN; IN VIVO STUDY; LYMPH NODE; LYMPHOCYTE; MULTIPLE SCLEROSIS; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING;

ADMINISTRATION, ORAL; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MULTIPLE SCLEROSIS; PREVALENCE; PROPYLENE GLYCOLS; RECEPTORS, LYSOSPHINGOLIPID; RISK ASSESSMENT; RISK FACTORS; SPHINGOSINE; TREATMENT OUTCOME;

EID: 79952432016     PISSN: 00282804     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00115-010-3075-8     Document Type: Article

References (75)

1. Aktas O, Smorodchenko A, Brocke S et al (2005) Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron 46:421-432 (Pubitemid 40616886)
2. Aktas O, Ullrich O, Infante-Duarte C et al (2007) Neuronal damage in brain inflammation. Arch Neurol 64:185-189
3. Balatoni B, Storch MK, Swoboda EM et al (2007) FTY720 sustains and restores neuronal function in the DA rat model of MOG-induced experimental autoimmune encephalomyelitis. Brain Res Bull 74:307-316 (Pubitemid 47368881)
4. Bartholomaus I, Kawakami N, Odoardi F et al (2009) Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462:94-104
5. Beer MS, Stanton JA, Salim K et al (2000) EDG receptors as a therapeutic target in the nervous system. Lysophospholipids and Eicosanoids Biol Pathophysiol 905:118-131 (Pubitemid 30255412)
6. Bennun A, Wekerle H, Cohen IR (1981) The Rapid Isolation of Clonable Antigen-Specific Lymphocyte-T Lines Capable of Mediating Autoimmune Encephalomyelitis. Eur J Immunol 11:195-199 (Pubitemid 11104096)
7. Brinkmann V (2009) FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol 158:1173-1182
8. Brinkmann V, Davis MD, Heise CE et al (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem 277:21453-21457 (Pubitemid 34952287)
9. Budde K, Schmouder RL, Brunkhorst R et al (2002) First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J Am Soc Nephrol 13:1073-1083 (Pubitemid 34274106)
10. Coelho RP, Payne SG, Bittman R et al (2007) The immunomodulator FTY720 has a direct cytoprotective effect in oligodendrocyte progenitors. J Pharmacol Exp Ther 323:626-635 (Pubitemid 350005137)
11. Cohen JA, Barkhof F, Comi G et al (2010) Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis. N Engl J Med 362:402-415
12. Dev KK, Mullershausen F, Mattes H et al (2008) Brain sphingosine-1- phosphate receptors: Implication for FTY720 in the treatment of multiple sclerosis. Pharmacol Ther 117:77-93 (Pubitemid 350192672)
13. Edsall LC, Pirianov GG, Spiegel S (1997) Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. J Neurosci 17:6952-6960 (Pubitemid 27427874)
14. Foster CA, Howard LM, Schweitzer A et al (2007) Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: Consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther 323:469-476 (Pubitemid 350005125)
15. Foster CA, Mechtcheriakova D, Storch MK et al (2009) FTY720 Rescue therapy in the dark agouti rat model of experimental autoimmune encephalomyelitis: expression of central nervous system genes and reversal of blood-brain-barrier damage. Brain Pathol 19:254-266
16. Fujino M, Funeshima N, Kitazawa Y et al (2003) Amelioration of experimental autoimmune encephalomyelitis in lewis rats by FTY720 treatment. J Pharmacol Exp Ther 305:70-77 (Pubitemid 36378136)
17. Fujita T, Inoue K, Yamamoto S et al (1994) Fungal Metabolites. A Potent Immunosuppressive Activity Found in Isaria-Sinclairii Metabolite. J Antibiot 47:208-215
18. Fukushima N, Ishii I, Contos JJA et al (2001) Lysophospholipid receptors. Annu Rev Pharmacol Toxicol 41:507-534 (Pubitemid 32385897)
19. Gardell SE, Dubin AE, Chun J (2006) Emerging medicinal roles for lysophospholipid signaling. Trends Mol Med 12:65-75 (Pubitemid 43202124)
20. Gergely P, Wallstrom E, Nuesslein-Hildesheim B et al (2009) Phase I study with the selective S1P1/S1P5 receptor modulator BAF312 indicates that S1P1 rather than S1P3 mediates transient heart rate reduction in humans. Mult Scler 15:S125-S126
21. Gold R, Linington C, Lassmann H (2006) Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129:1953-1971 (Pubitemid 44289062)
22. Greter M, Heppner FL, Lemos MP et al (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11:328-334 (Pubitemid 40460562)
23. Harada J, Foley M, Moskowitz MA, Weber C (2004) Sphingosine-1-phosphate induces proliferation and morphological changes of neural progenitor cells. J Neurochem 88:1026-1039 (Pubitemid 38199325)
24. Hartung HP (2009) New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab. Lancet Neurol 8:28-31
25. Hartung HP, Aktas O (2009) Bleak prospects for primary progressive multiple sclerosis therapy: downs and downs, but a glimmer of hope. Ann Neurol 66:429-432
26. Hartung HP, Aktas O (2010) Oral therapies for multiple sclerosis: are we there yet? Lancet Neurol 9:454-457
27. Hartung HP, Kieseier BC, Aktas O (2010) Cladribin. Nervenarzt 81:194-202
28. Horga A, Montalban X (2008) FTY720 (fingolimod) for relapsing multiple sclerosis. Expert Rev Neurother 8:699-714 (Pubitemid 351656821)
29. Jung CG, Kim HJ, Miron VE et al (2007) Functional consequences of S1P receptor modulation in rat oligodendroglial lineage cells. Glia 55:1656-1667 (Pubitemid 47612852)
30. Kappos L, Antel J, Comi G et al (2006) Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 355:1124-1140 (Pubitemid 44394919)
31. Kataoka H, Sugahara K, Shimano K et al (2005) FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration. Cell Mol Immunol 2:439-448
32. Kimura A, Ohmori T, Ohkawa R et al (2007) Essential roles of sphingosine 1-phosphate/S1P(1) receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells 25:115-124 (Pubitemid 46052981)
33. Kovarik JM, Schmouder RL, Hartmann S et al (2006) Fingolimod (FTY720) in severe hepatic impairment: Pharmacokinetics and relationship to markers of liver function. J Clin Pharmacol 46:149-156 (Pubitemid 43146445)
34. Kremer D, Heinen A, Jadasz J et al (2009) p57kip2 is dynamically regulated in experimental autoimmune encephalomyelitis and interferes with oligodendroglial maturation. Proc Natl Acad Sci U S A 106:9087-9092
35. Krishnamoorthy G, Saxena A, Mars LT et al (2009) Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis. Nat Med 15:626-632
36. Leypoldt F, Munchau A, Moeller F et al (2009) Hemorrhaging focal encephalitis under fingolimod (Fty720) treatment: a case report. Neurology 72:1022-1024
37. Mandala S, Hajdu R, Bergstrom J et al (2002) Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296:346-349 (Pubitemid 34303689)
38. Matloubian M, Lo CG, Cinamon G et al (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355-360 (Pubitemid 38133663)
39. Mehling M, Brinkmann V, Antel J et al (2008) FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology 71:1261-1267
40. Menn B, Garcia-Verdugo JM, Yaschine C et al (2006) Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 26:7907-7918 (Pubitemid 44315160)
41. Miron VE, Darlington PJ, Ludwin SK et al (2009) The immunomodulator fingolimod (FTY720) increases myelin production following demyelination of organotypic cerebellar slices. Neurology 72:A421
42. Miron VE, Hall JA, Kennedy TE et al (2008) Cyclical and dose-dependent responses of adult human mature oligodendrocytes to fingolimod. Am J Pathol 173:1143-1152
43. Miron VE, Jung CG, Kim HJ et al (2008) FTY720 modulates human oligodendrocyte progenitor process extension and survival. Ann Neurol 63:61-71 (Pubitemid 351240552)
44. Miron VE, Schubart A, Antel JP (2008) Central nervous system-directed effects of FTY720 (fingolimod). J Neurol Sci 274:13-17
45. Mizugishi K, Yamashita T, Olivera A et al (2005) Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol 25:11113-11121 (Pubitemid 41747151)
46. Moore AN, Kampfl AW, Zhao X et al (1999) Sphingosine-1-phosphate induces apoptosis of cultured hippocampal neurons that requires protein phosphatases and activator protein-1 complexes. Neuroscience 94:405-415 (Pubitemid 29436069)
47. Mullershausen F, Craveiro LM, Shin Y et al (2007) Phosphorylated FTY720 promotes astrocyte migration through sphingosine-1-phosphate receptors. J Neurochem 102:1151-1161 (Pubitemid 47174238)
48. Mullershausen F, Zecri F, Cetin C et al (2009) Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol 5:428-434
49. Novgorodov AS, El-Alwani M, Bielawski J et al (2007) Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration. FASEB J 21:1503-1514 (Pubitemid 46684852)
50. O'Connor P, Comi G, Montalban X et al (2009) Oral fingolimod (FTY720) in multiple sclerosis. Two-year results of a phase II extension study. Neurology 72:73-79
51. Osinde M, Mullershausen F, Dev KK (2007) Phosphorylated FTY720 stimulates ERK phosphorylation in astrocytes via S1P receptors. Neuropharmacology 52:1210-1218 (Pubitemid 46546406)
52. Papadopoulos D, Rundle J, Patel R et al (2010) FTY720 Ameliorates MOG-induced experimental autoimmune encephalomyelitis by suppressing both cellular and humoral immune responses. J Neurosci Res 88:346-359
53. Pebay A, Toutant M, Premont J et al (2001) Sphingosine-1-phosphate induces proliferation of astrocytes: regulation by intracellular signalling cascades. Eur J Neurosci 13:2067-2076 (Pubitemid 32664301)
54. Picard-Riera N, Decker L, Delarasse C et al (2002) Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice. Proc Natl Acad Sci U S A 99:13211-13216
55. Postma FR, Jalink K, Hengeveld T, Moolenaar WH (1996) Sphingosine-1-phosphate rapidly induces Rho-dependent neurite retraction: Action through a specific cell surface receptor. EMBO J 15:2388-2392 (Pubitemid 26151178)
56. Prozorovski T, Schulze-Topphoff U, Glumm R et al (2008) Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat Cell Biol 10:385-394
57. Ransohoff RM (2006) EAE: pitfalls outweigh virtues of screening potential treatments for multiple sclerosis. Trends Immunol 27:167-168
58. Rausch M, Hiestand P, Foster CA et al (2004) Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: Clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. J Magn Reson Imaging 20:16-24 (Pubitemid 38857512)
59. Rouach N, Pebay A, Meme W et al (2006) S1P inhibits gap junctions in astrocytes: involvement of G(i) and Rho GTPase/ROCK. Eur J Neurosci 23:1453-1464
60. Sanna MG, Liao JY, Jo EJ et al (2004) Sphingosine 1-phosphate (S1P) receptor subtypes S1P(1) and S1P(3), respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem 279:13839-13848 (Pubitemid 38468916)
61. Schmouder R, Serra D, Wang YB et al (2006) FTY720: Placebo-controlled study of the effect on cardiac rate and rhythm in healthy subjects. J Clin Pharmacol 46:895-904 (Pubitemid 44050826)
62. Schulze-Topphoff U, Prat A, Prozorovski T et al (2009) Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system. Nat Med 15:788-793
63. Schwab SR, Cyster JG (2007) Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol 8:1295-1301 (Pubitemid 350131168)
64. Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638-647
65. Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: An enigmatic signalling lipid. Nat Rev Mol Cell Biol 4:397-407 (Pubitemid 36565571)
66. Steinman L, Zamvil SS (2005) Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends Immunol 26:565-571 (Pubitemid 41726443)
67. Stromnes IM, Goverman JM (2006) Active induction of experimental allergic encephalomyelitis. Nat Protoc 1:1810-1819 (Pubitemid 46773300)
68. Takabe K, Paugh SW, Milstien S, Spiegel S (2008) "Inside-Out" signaling of sphingosine-1-phosphate: Therapeutic targets. Pharmacol Rev 60:181-195 (Pubitemid 351962008)
69. Teshima K, Imayoshi T, Matsura M (1995) FTY720, a novel immunosuppressant, possessing unique mechanisms. III. Pharmacological activities in several autoimmune and inflammatory models. Abstracts of the 9th International Congress of Immunology, San Fransisco 5172
70. Toman RE, Payne SG, Watterson KR et al (2004) Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension. J Cell Biol 166:381-392 (Pubitemid 39031241)
71. Webb M, Tharn CS, Lin FF et al (2004) Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol 153:108-121 (Pubitemid 38950933)
72. Yanagawa Y, Sugahara K, Kataoka H et al (1998) FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. II. FTY720 prolongs skin allograft survival by decreasing T cell infiltration into grafts but not cytokine production in vivo. J Immunol 160:5493-5499 (Pubitemid 28267841)
73. McDonald et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121-127
74. Polman CH, Reingold SC, Edan G et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the"McDonald Criteria". Ann Neurol 58: 840-846 (Pubitemid 41746873)
75. Aktas O, Kieseier B, Hartung HP (2010). Neuroprotection, regeneration and immunomodulation: broadening the therapeutic repertoire in multiple sclerosis. Trends Neurosci 33:140-152