Pharmacological modulation of peripheral T and B lymphocytes by a selective sphingosine 1-phosphate receptor-1 modulator

Journal of Clinical Pharmacology

Volumn 52, Issue 7, 2012, Pages 996-1006

  Moberly, James B ^a   Rohatagi, Shashank ^a   Zahir, Hamim ^a   Hsu, Ching ^a   Noveck, Robert J ^b   Truitt, Kenneth E ^a  

^a DAIICHI SANKYO INC   (United States)

^b DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

autoimmune diseases; B cells; bradycardia; CD4; CD8; CS 0777; lymphopenia; multiple sclerosis; S1P receptor modulator

Indexed keywords

1 [5 (3 AMINO 4 HYDROXY 3 METHYLBUTYL) 1 METHYL 1H PYRROL 2 YL] 4 (4 METHYLPHENYL)BUTAN 1 ONE; CS 0777; CS 0777P; IMMUNOMODULATING AGENT; PLACEBO; UNCLASSIFIED DRUG;

ADULT; ARTICLE; B LYMPHOCYTE; BRADYCARDIA; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; COHORT ANALYSIS; CONTROLLED STUDY; DIASTOLIC BLOOD PRESSURE; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; HEADACHE; HUMAN; HUMAN EXPERIMENT; HYPERTRANSAMINASEMIA; LEUKOCYTE COUNT; LYMPHOCYTE COUNT; MALE; NEUTROPHIL COUNT; NORMAL HUMAN; PAPULOVESICULAR RASH; PHASE 1 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT;

ADULT; AMINO ALCOHOLS; B-LYMPHOCYTES; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HUMANS; LYMPHOCYTE COUNT; MALE; PYRROLES; RECEPTORS, LYSOSPHINGOLIPID; YOUNG ADULT;

EID: 84862803586     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270011408728     Document Type: Article

References (46)

1. Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signaling lipid. Nat Rev Mol Cell Biol. 2003;4:397-407.
2. Cyster JG. Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu Rev Immunol. 2005;23:127-159. (Pubitemid 40563167)
3. Rosen H, Goetzl EJ. Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol. 2005;5:560-570. (Pubitemid 40961333)
4. Rosen H, Gonzalez-Cabrera P, Marsolais D, Cahalan S, Don AS, Sanna MG. Modulating tone: the overture of S1P receptor immunotherapeutics. Immunol Rev. 2008;223:221-235. (Pubitemid 351986190)
5. Rivera J, Proia RL, Olivera A. The alliance of sphingosine-1-phosphate and its receptors in immunity. Nat Rev Immunol. 2008;8:753-763.
6. Brinkmann V, Davis MD, Heise CE, et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002;277:21453-21457. (Pubitemid 34952287)
7. Brinkmann V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther. 2007;115:84-105. (Pubitemid 46990553)
8. Brinkmann V, Billich A, Baumruker T, et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010;9:883-897.
9. Chiba K. FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors. Pharmacol Ther. 2005;108:308-319. (Pubitemid 41691870)
10. Matloubian M, Lo CG, Cinamon G, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427:355-360. (Pubitemid 38133663)
11. Brinkmann V, Cyster JG, Hla T. FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant. 2004;4:1019-1025. (Pubitemid 38868590)
12. Matsuura M, Imayoshi T, Okumoto T. Effect of FTY720, a novel immunosuppressant, on adjuvant- and collagen-induced arthritis in rats. Int J Immunopharm. 2000;22:323-331. (Pubitemid 30109509)
13. Daniel C, Sartory N, Zahn N, Geisslinger G, Radeke HH, Stein JM. FTY720 ameliorates Th1-mediated colitis in mice by directly affecting the functional activity of CD4+CD25+ regulatory T cells. J Immunol. 2007;178:2458-2468. (Pubitemid 46233446)
14. Fujino M, Funeshima N, Kitazawa Y, et al. Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. J Pharmacol Exp Ther. 2003;305:70-77. (Pubitemid 36378136)
15. Webb M, Tham C-S, Lin F-F, et al. Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol. 2004;153: 108-121. (Pubitemid 38950933)
16. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362:402-415.
17. Kappos L, Radue E-W, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362:387-401.
18. Kappos L, Antel J, Comi G, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006;355:1124-1140. (Pubitemid 44394919)
19. Shimozato T, Tomisato W, Doi H, et al. Preclinical evaluation of a selective sphingosine 1-phospate receptor-1 modulator: in vitro binding selectivity and effects on experimental autoimmune encephalomyelitis in rats. Mult Scler. 2009;15:S78.
20. Inaba SI, Tanaka K, Tomisato W, et al. Exposure-response analysis of CS-0777, a sphingosine 1-phosphate receptor modulator, in preclinical models. Mult Scler. 2009;15:S78.
21. Rohatagi S, Zahir H, Moberly JB, et al. Use of an exposure-response model to aid early drug development of an oral sphingosine 1-phosphate receptor modulator. J Clin Pharmacol. 2009;49:50-62.
22. Ilson B. Cardiovascular monitoring in normal healthy adults: a literature review and recommendations for the reporting of disturbances of cardiac rhythm. Am J Ther. 1995;2:893-899.
23. Budde K, Schmouder RL, Brunkhorst R, et al. First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J Am Soc Nephrol. 2002;13:1073-1083. (Pubitemid 34274106)
24. Schmouder R, Serra D, Wang Y, et al. FTY720: placebo-controlled study of the effect on cardiac rate and rhythm in healthy subjects. J Clin Pharmacol. 2006;46:895-904. (Pubitemid 44050826)
25. Sanna MG, Liao J, Jo E, et al. Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004;279(12):13839-13848. (Pubitemid 38468916)
26. Forrest M, Sun S-Y, Hajdu R, et al. Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004;309:758-768. (Pubitemid 38542632)
27. Miron VE, Hall JA, Kennedy TE, Soliven B, Antel JP. Cyclical and dose-dependent responses of adult human mature oligodendrocytes to fingolimod. Am J Pathol. 2008;173:1143-1152.
28. Miron VE, Jung CG, Kim HJ, Kennedy TE, Soliven B, Antel JP. FTY720 modulates human oligodendrocyte progenitor process extension and survival. Ann Neurol. 2008;63:61-71. (Pubitemid 351240552)
29. Mullershausen F, Zecri F, Cetin C, Billich A, Guerini D, Seuwen K. Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol. 2009;5:428-434.
30. Rajagopal S, Rajagopal K, Lefkowitz RJ. Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat Rev Drug Discov. 2010;9:373-386.
31. Sensken S-C, Bode C, Gräler MH. Accumulation of fingolimod (FTY720) in lymphoid tissues contributes to prolonged efficacy. J Pharmacol Exp Ther. 2009;328:963-969.
32. Gergely P, Wallström E, Nuesslein-Hildesheim B, et al. 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. 2009;15:S125.
33. Cusack KP, Stoffel RH. S1P1 receptor agonists: assessment of selectivity and current clinical activity. Curr Opin Drug Disc Devel. 2010;13:481-488.
34. Kovarik JM, Riviere G-J, Neddermann D, Maton S, Hunt TL, Schmouder RL. A mechanistic study to assess whether isoproterenol can reverse the negative chronotropic effect of fingolimod. J Clin Pharm. 2008;48:303-310. (Pubitemid 351257776)
35. Kovarik JM, Slade A, Riviere G-J, et al. The ability of atropine to prevent and reverse the negative chronotropic effect of fingolimod in healthy subjects. Br J Clin Pharmacol. 2008;66:199-206.
36. Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of the oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362:416-426.
37. Zahir H, Moberly J, Carothers TJ, et al. Application of modeling and simulation in early clinical evaluation of an S1P1 receptor modulator for treatment of multiple sclerosis. Mult Scler. 2009;15:S244.
38. Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008;358:676-88. (Pubitemid 351240747)
39. Budde K, Schmouder RL, Nashan B, et al. Pharmacodynamics of single doses of the novel immunosuppressant FTY720 in stable renal transplant patients. Am J Transplant. 2003;3:846-854. (Pubitemid 36827906)
40. Kovarik JM, Schmouder R, Barilla D, Riviere G-J, Wang Y, Hunt T. Multiple-dose FTY720: tolerability, pharmacokinetics, and lymphocyte responses in healthy subjects. J Clin Pharmacol. 2004;44:532-537. (Pubitemid 38509722)
41. Vaessen LMB, van Besouw NM, Mol WM, Ijzermans JNM, Weimar W. FTY720 treatment of kidney transplant patients: a differential effect on B cells, naïve T cells, memory T cells and NK cells. Transpl Immunol. 2006;15:281-288.
42. Tedesco-Silva H, Mourad G, Kahan BD, et al. FTY720, a novel immunomodulator: efficacy and safety results from the first phase 2A study in de novo renal transplantation. Transplantation. 2005;79:1553-1560. (Pubitemid 40847587)
43. Mehling M, Brinkmann V, Antel J, et al. FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology. 2008;71:1261-1267.
44. Mehling M, Lindberg R, Raulf F, et al. Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. Neurology. 2010;75:403-410.
45. Sim-Selley LJ, Goforth PB, Mba MU, et al. Sphingosine-1-phosphate receptors mediate neuromodulatory functions in the CNS. J Neurochem. 2009;110:1191-1202.
46. Moberly J, Rohatagi S, Zahir H, Hsu C, Noveck R, Truitt K. Early clinical evaluation of an S1P1 receptor modulator for treatment of multiple sclerosis: results from a single ascending dose phase 1 study in healthy volunteers. Mult Scler. 2009;15:S244.