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Treatment of Multiple Sclerosis with Cyclosporine A

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Treatment of Multiple Sclerosis

Part of the book series: Clinical Medicine and the Nervous System ((CLIN.MED.NERV.))

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Abstract

Cyclosporine A (cyclosporine) is a cyclic peptide representative of a powerful new class of drugs characterized by semi-selective effects on specific lymphocyte populations. As a prototype agent, cyclosporine has proven effective in preventing host versus graft and graft versus host responses when used as monotherapy or when combined with conventional immunosuppressive agents. As a result, cyclosporine has dramatically altered current approaches to organ transplantation (Kahan 1989). Cyclosporine has increasingly also been reported to be useful in controlling a variety of putative autoimmune diseases of man (reviewed in Bach 1989). Given the proven efficacy of the drug in several model autoimmune diseases of animals, cyclosporine has become an attractive candidate for testing in those human neurological diseases with presumed major immunopathogenic components. This chapter focuses on the pharmacology and immunopharmacology of cyclosporine as applied to man, proposed mechanisms of the immunomodulatory effects of the drug and the known systemic and neural toxicity of the molecule, and reviews the effects of cyclosporines on autoimmune neurological disease models. The results of studies of the use of cyclosporine in multiple sclerosis (MS) are considered in detail.

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References

  • Bach, JF (1989) Cyclosporine in autoimmune diseases. Transplant Proc 21: 97–113

    PubMed  CAS  Google Scholar 

  • Bania MB, AnteI JP, Reder AT, Nicholas MK, Arnason BG (1986) Suppressor and cytolytic cell function in multiple sclerosis. Effects of cyclosporine A and interleukin 2. J Clin Invest 78: 582–586

    Article  PubMed  CAS  Google Scholar 

  • Bierer BE, Somers PK, Wandless TJ, Burakoff SJ, Schreiber SL (1990) Probing immunosuppressant action with a nonnatural immunophilin ligand. Science 250: 556–559

    Article  PubMed  CAS  Google Scholar 

  • Borel JF (1989) Pharmacology of cyclosporine (Sandimmune). IV. Pharmacological properties in vivo. Pharmacol Rev 41: 259–370

    CAS  Google Scholar 

  • Calder VL, Bellamy AS, Owen S et al. (1987) Effects of cyclosporin A on expression of IL-2 and IL-2 receptors in normal and multiple sclerosis patients. Clin Exp Immunol 70: 570–577

    PubMed  CAS  Google Scholar 

  • Carrier M, Wild J, Pelletier LC, Copeland JG (1990) Bromocriptine as an adjuvant to cyclosporine immunosuppression after heart transplantation. Ann Thoracic Surg 49: 129–132

    Article  CAS  Google Scholar 

  • Cockburn IT, Krupp P (1989) The risk of neoplasms in patients treated with cyclosporne A. J Autoimmun 2: 723–731

    Article  PubMed  CAS  Google Scholar 

  • Colombani PM, Hess AD (1987) T-lymphocyte inhibition by cyclosporine. Potential mechanisms. Biochem Pharmacol 36: 3789–3793

    Article  PubMed  CAS  Google Scholar 

  • DeGroen PC, Aksamit AJ, Rakela J, Forbes GS, Krom RAF (1987) Central nervous system toxicity after liver transplantation. The role of cyclosporine and cholesterol. N Engl J Med 317: 861–866

    Google Scholar 

  • DiPadova FE (1989) Pharmacology of cyclosporine (Sandimmune). V. Pharmacological effects on immune function — In vitro studies. Pharmacol Rev 41: 373–405

    CAS  Google Scholar 

  • Ellerman KE, Powers JM, Brostoff SW (1988) A suppressor T-lymphocyte cell line for autoimmune encephalomyelitis. Nature 331: 265–267

    Article  PubMed  CAS  Google Scholar 

  • Ellison GW, Myers LW, Mickey MR et al. (1989) A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis. Neurology 39: 1018–1026

    PubMed  CAS  Google Scholar 

  • Emmel EA, Verweij CL, Durand DB, Higgins KM, Lacy E, Crabtree GR (1989) Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science 246: 1617–1620

    Article  PubMed  CAS  Google Scholar 

  • Famiglio L, Racusen L, Fivush B, Solez K, Fisher R (1989) Central nervous system toxicity of cyclosporine in a rat model. Transplantation 48: 316–321

    Article  PubMed  CAS  Google Scholar 

  • Fischer G, Wittmannlieboid B, Lang K, Kiefhaber T, Schmid FX (1989) Cyclophilin and peptidylprolyl cis-trans isomerase are probably identical proteins. Nature 337: 476–478

    Article  PubMed  CAS  Google Scholar 

  • Forstermann U, Kuhn K, Vesterqvist O et al. (1989) An increase in the ratio of thromboxane A2 to prostacyclin in association with increased blood pressure in patients on cyclosporine A. Prostaglandins 37: 567–575

    Article  PubMed  CAS  Google Scholar 

  • Handschumacher RE, Harding MW, Rice J, Drugge RJ (1984) Cyclophilin: A specific cytosolic binding protein for cyclosporin A. Science 544–547

    Google Scholar 

  • Hess AD (1985) Effect of interleukin 2 on the immunosuppressive action of cyclosporine. Transplantation 39: 62–68

    Article  PubMed  CAS  Google Scholar 

  • Hughes RAC, McPherson K, British-Dutch MS Azathioprine Trial Group (1988) Double-masked trial of azathioprine in multiple sclerosis. Lancet 2: 170–183

    Google Scholar 

  • Kahan BD (1989) Cyclosporine. N Engi J Med 321: 1725–1739

    Article  CAS  Google Scholar 

  • Kappos L, Patzold U, Dommasch D et al. (1988a) Cyclosporine versus azathioprine in the longterm treatment of multiple sclerosis: Results of the German multicenter study. Ann Neurol 23: 56–63

    Google Scholar 

  • Kappos L, Stadt D, Ratzka M et al. (1988b) Magnetic resonance imaging in the evaluation of treatment in multiple sclerosis. Neuroradiology 30: 299–302

    Article  PubMed  CAS  Google Scholar 

  • Kelley VE, Kirkman RL, Bastos M, Barrett LV, Strom TB (1989) Enhancement of immunosuppression by substitution of fish oil for olive oil as a vehicle for cyclosporine. Transplantation 48: 98–102

    Article  PubMed  CAS  Google Scholar 

  • Kerman RH, Wolinsky JS, Nath A, Sears ES Jr, Franklin GM, Nelson LM (1987) Immune regulation in multiple sclerosis patients treated with cyclosporine. Ann Neurol 22: 154

    Google Scholar 

  • Kerman RH, Wolinsky JS, Nath A, Sears ES Jr (1988) Serial immune evaluation of cyclosporineand placebo-treated multiple sclerosis patients. J Neuroimmunol 18: 325–331

    Article  PubMed  CAS  Google Scholar 

  • Kim JH, Perfect JR (1989) Infection and cyclosporine. Rev Infect Dis 11: 677–690

    Article  PubMed  CAS  Google Scholar 

  • Krupp P, Timonen P, Gulich A (1985) Side effects and safety of Sandimmune in long-term treatment In: R Schindler (ed) Ciclosporin in Autoimmune Diseases. Springer-Verlag, Berlin, pp 41–49

    Google Scholar 

  • McLean BN, Rudge P, Thompson EJ (1989) Cyclosporin A curtails the progression of free light chain synthesis in the CSF of patients with multiple sclerosis. J Neurol Neurosurg Psych 52: 529–531

    Article  CAS  Google Scholar 

  • Mihatsch MJ, Thiel G, Ryffel B (1985) Ciclosporin-associated nephropathy In: R Schindler (ed) Ciclosporin in Autoimmune Diseases. Springer-Verlag, Berlin, pp 50–58

    Google Scholar 

  • Multiple Sclerosis Study Group (1990) Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: A randomized, double-blinded, placebo-controlled clinical trial. Ann Neurol 27: 591–605

    Article  Google Scholar 

  • Palestine AG, Austin III HA, Balow JE et al. (1986) Renal histopathologic alterations in patients treated with cyclosporine for uveitis. N Engl J Med 314: 1293–1298

    Article  PubMed  CAS  Google Scholar 

  • Palestine AG, Muellenberg-Coulombre CG, Kim MK, Gelato MC, Nussenblatt RB (1987) Bromocriptine and low dose cyclosporine in the treatment of experimental autoimmune uveitis in the rat. J Clin Invest 79: 1078–1081

    Article  PubMed  CAS  Google Scholar 

  • Patzold U, Dommasch D, Poser S et al. (1985) The effect of ciclosporin versus azathioprine on the course of multiple sclerosis; Design of a long-term follow-up study and side effects In: R Schindler (ed) Ciclosporin in Autoimmune Diseases. Springer-Verlag, Berlin, pp 88–95

    Google Scholar 

  • Pender MP, Stanley GP, Yoong G, Nguyen KB (1990) The neuropathology of chronic relapsing experimental allergic encephalomyelitis induced in the Lewis rat by inoculation with whole spinal cord and treatment with cyclosporin A. Acta Neuropath 80: 172–183

    Article  PubMed  CAS  Google Scholar 

  • Quesniaux VFJ (1989) Pharmacology of cyclosporine (Sandimmune). III. Immunochemistry and monitoring. Pharm Rev 41: 249–258

    CAS  Google Scholar 

  • Rich S, Carpino MR, Arhelger C (1984) Suppressor T cell growth and differentiation: Identification of a cofactor required for suppressor T cell function and distinct from interleukin 2. J Exp Med 1473–1490

    Google Scholar 

  • Rubin AM, Kang H (1987) Cerebral blindness and encephalopathy with cyclosporin. Neurology 37: 1072–1076

    PubMed  CAS  Google Scholar 

  • Rudge P (1985) The use of ciclosporin (CyA) in multiple sclerosis — Trial design and tolerance. In: R Schindler (ed) Ciclosporin in Autoimmune Diseases. Springer-Verlag, Berlin, pp 83–87 Rudge P (1990) Cyclosporine and multiple sclerosis In: SD Cook (ed) Handbook of Multiple Sclerosis. Marcel Dekker Inc, New York, pp 439–456

    Google Scholar 

  • Rudge P, Koetsier JC, Mertin J et al. (1989) Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiarry 52: 559–565

    Article  CAS  Google Scholar 

  • Ryffel B (1989) Pharmacology of cyclosporine. VI. Cellular activation — Regulation of intracellular events by cyclosporine. Pharmacol Rev 41: 407–422

    CAS  Google Scholar 

  • Scherrer U, Vissing SF, Morgan BJ et al. (1990) Cyclosporine-induced sympathetic activation and hypertension after heart transplantation. N Engl J Med 323: 693–699

    Article  PubMed  CAS  Google Scholar 

  • Scoble JE, Senior JCM, Chan P, Varghese Z, Sweny P, Moorhead JF (1989) In vitro cyclosporine toxicity the effect of verapamil. Transplantation 47: 647–650

    Article  PubMed  CAS  Google Scholar 

  • Thompson CB, June CH, Sullivan KM, Thomas ED (1984) Association between cyclosporin neurotoxicity and hypomagnesaemia. Lancet 2: 116–1120

    Google Scholar 

  • Trotter JL, van der Veen RC, Clifford DB (1990) Serial studies of serum interleukin-2 in chronic progressive multiple sclerosis patients: Occurrence of `bursts’ and effect of cyclosporine. J Neuroimmunol 28: 9–14

    Google Scholar 

  • Whisler RL, Lindsey JA, Proctor KVW, Morisaki N, Cornwell DG (1984) Characteristics of cyclosporine induction of increased prostaglandin levels from human peripheral blood monocytes. Transplantation 38: 377–381

    Article  PubMed  CAS  Google Scholar 

  • Whitham RH, Vandenbark AA, Bourdette DN, Chou YK, Offner H (1990) Suppressor cell regulation of encephalitogenic T cell lines: Generation of suppressor macrophages with cyclosporin A and myelin basic protein. Cell Immunol 126: 290–303

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Jerry S. Wolinsky
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Editors and Affiliations

  1. Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195-5244, Cleveland, OH, USA

    Richard A. Rudick MD  & Donald E. Goodkin MD  & 

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© 1992 Springer-Verlag London Limited

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Wolinsky, J.S. (1992). Treatment of Multiple Sclerosis with Cyclosporine A. In: Rudick, R.A., Goodkin, D.E. (eds) Treatment of Multiple Sclerosis. Clinical Medicine and the Nervous System. Springer, London. https://doi.org/10.1007/978-1-4471-3184-7_10

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  • DOI: https://doi.org/10.1007/978-1-4471-3184-7_10

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-3186-1

  • Online ISBN: 978-1-4471-3184-7

  • eBook Packages: Springer Book Archive

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