Summary
Copolymer 1 (Cop 1), a synthetic copolymer of amino acids, is very effective in suppression of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis (MS). Cop 1 was found incapable of inducing EAE, yet it suppressed EAE in a variety of animal species, including primates. The immunological cross-reaction between the myelin basic protein (MBP) and Cop 1 serves as the basis for the suppressive activity of Cop 1 in EAE, by the induction of antigen-specific suppressor cells and competition with MBP for binding to major histocompatibility complex (MHC) molecules. Clinical trials with Cop 1, both Phase II and Phase III, were performed in relapsing-remitting (E-R) patients. The latter, a two-year multi-center double blind trial with 251 participating patients was conducted at 11 leading medical centers in the USA. It demonstrated a significant beneficial effect of Cop 1 in both diminishing the rate of exacerbations and improving the clinical status. The side effects of Cop 1 were only minimal. The cumulative results indicate that Cop 1 is a promising candidate drug for multiple sclerosis.
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References
Abramsky O, Teitelbaum D, Arnon R (1977) Effect of a synthetic polypeptide (Cop 1) on patients with multiple sclerosis and with acute disseminated encephalomyelitis. J Neurol Sci 31: 433–438
Aharoni R, Teitelbaum D, Arnon R (1993) T-suppressor hybridomas and IL-2 dependent lines induced by copolymer 1 or by spinal cord homogenate down regulate experimental allergic encephalomyelitis. Eur J Immunol 23: 17–25
Aharoni R, Teitelbaum D, Sela M, Arnon R (1996) Copolymer 1 induces suppressor T cells of the Th2 type. J Neurol 243 [Suppl 2]: S17
Arnon R (1981) Experimental allergic encephalomyelitis-susceptibility and suppression. Immunol Rev 55: 5–30
Bernard CCA, Kerlero de Rosbo N (1992) Multiple sclerosis an autoimmune disease of multifunctional etiology. Curr Opin Immunol 2: 760–765
Ben-Nun A, Mendel I, Bakimeer R, Fridkis-Hareli M, Teitelbaum D, Arnon R, Sela M, Kerlero de Rosbo N (1996) The autoimmune reactivity to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis is potentially pathogenic: effect of Copolymer 1 on MOG-induced disease. J Neurol 43 [Suppl 1]: S14–S22
Bornstein MB, Miller AJ, Teitelbaum D, Arnon R, Sela M (1982) Multiple sclerosis: trial of a synthetic polypeptide. Ann Neurol 11: 317–319
Bornstein MB, Miller A, Slagle S, Weitzman M, Crystal H, Drexler E, Keilson M, Merriam A, Wassertheil-Smoller S, Spada V, Weiss W, Arnon R, Jacobsohn I, Teitelbaum D, Sela M (1987) A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med 317: 408–414
Fridkis-Hareli, M, Teitelbaum D, Gurevich E, Pecht I, Brautbar C, Oh Joong K, Brenner T, Arnon R, Sela M (1994) Direct binding of myelin basic protein and synthetic copolymer 1 to class II major histocompatibility complex molecules on living antigen presenting cells-specificity and promiscuity. Proc Natl Acad Sci US 91: 4872–4876
Johnson KP, Brooks, BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Pannitch HS, Rose JW, Schiffer RB, Vollmer T, Weiner LP, Wolinsky JC (1995) Copolymer 1 reduces relapse rate and improves disability in relapsing — remitting multiple sclerosis. Results of a phase III multicenter double blind, placebo-controlled trial. Neurology 1: 65–70
Johnson KP, The Copolymer 1 Multiple Sclerosis Study Group (1996) Extended report of the positive multicenter phase III trial of copolymer 1 for the treatment of relapsing remitting multiple sclerosis. Neurology 46: A406
Keith AB, Arnon R, Teitelbaum D, Caspary EA, Wisniewski HM (1979) The effect of Cop 1, a synthetic polypeptide, on chronic relapsing experimental allergic encephalomyelitis in guinea pigs. J Neurol Sci 42: 267–274
Lando Z, Teitelbaum D, Arnon R (1979) Effect of cyclophosphamide on suppressor cell activity in mice unresponsive to EAE. J Immunol 123: 2156–2160
Lando Z, Teitelbaum D, Arnon R (1981) The immunological response in mice unresponsive to experimental allergic encephalomyelitis. J Immunol 126: 1526–1528
Lando Z, Dori Y, Teitelbaum D, Arnon R (1981) Unresponsiveness to experimental allergic encephalomyelitis in mice-replacement of suppressor cells by a soluble factor. J Immunol 127: 1915–1919
Sela M, Arnon R, Teitelbaum D (1990) Suppressive activity of Cop 1 in EAE and its relevance to multiple sclerosis. Bull Inst Pasteur 88: 303–314
Teitelbaum D, Meshorer A, Hirshfeld T, Arnon R, Sela M (1971) Suppression of experimental allergic encephalomyelitis by a synthetic basic copolymer. Eur J Immunol 1: 242–248
Teitelbaum D, Webb C, Meshorer A, Arnon R, Sela M (1973) Suppression by several synthetic polypeptides of experimental allergic encephalomyelitis induced in guinea pigs and rabbits with bovine and human basic encephalitogen. Eur J Immunol 3: 273–279
Teitelbaum D, Webb C, Bree M, Meshorer A, Arnon R, Sela M (1974) Suppression of experimental allergic encephalomyelitis in rhesus monkeys by a synthetic basic copolymer. Clin Immunol Immunopathol 3: 256–262
Teitelbaum D, Meshorer A, Arnon R (1977) Suppression of experimental allergic encephalomyelitis in baboons by Cop 1. Israel J Med Sci 13: 1038
Teitelbaum D, Aharoni R, Arnon R, Sela M (1988) Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1. Proc Natl Acad Sci USA 85: 9724–9728
Teitelbaum D, Aharoni R, Sela M, Arnon R (1991) Cross reactions and specificities of monoclonal antibodies against myelin basic protein and against the synthetic copolymer 1. Proc Natl Acad Sci USA 88: 9528–9532
Teitelbaum D, Milo R, Arnon R, Sela M (1992) Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic protein. Proc Natl Acad Sci USA 89: 137–141
Teitelbaum D, Fridkis-Hareli M, Arnon R, Sela M (1996) Copolymer 1 inhibits the onset of chronic relapsing experimental autoimmune encephalomyelitis and interferes with T cell responses to encephalitogenic peptides of myelin proteolipid protein. J Neuroimmunol 64: 209–217
Waksman BH (1985) Mechanisms in multiple sclerosis. Nature 318: 104–105
Webb C, Teitelbaum D, Arnon R, Sela M (1973) In vivo and in vitro immunological cross-reactions between basic encephalitogen and synthetic basic polypeptides capable of suppressing experimental allergic encephalomyelitis. Eur J Immunol 3: 279–286
Webb C, Teitelbaum D, Herz A, Arnon R, Sela M (1976) Molecular requirements involved in suppression of EAE by synthetic basic copolymers of amino acids. Immunochemistry 13: 333–337
Wisniewski HM, Keith AB (1977) Chronic relapsing experimental allergic encephalomyelitis: an experimental model of multiple sclerosis. Ann Neurol 1: 144–148
Zamvil SS, Steinman L (1990) The T lymphocyte in experimental allergic encephalomyelitis. Ann Rev Immunol 8: 579–621
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Teitelbaum, D., Arnon, R., Sela, M. (1997). Cop 1 as a candidate drug for multiple sclerosis. In: Mizuno, Y., Youdim, M.B.H., Calne, D.B., Horowski, R., Poewe, W., Riederer, P. (eds) Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6844-8_9
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DOI: https://doi.org/10.1007/978-3-7091-6844-8_9
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