rizvi et al were found. According to the manufacturer, rare cases of non-fatal anaphylaxis have also been reported. Sixty-six non-fatal anaphylactic reactions in about 80 000 treated patients have been reported worldwide (Rauschka et al 2005). GA is a pregnancy category B drug. Although its use is not recommended in pregnancy, there is no evidence to suggest increased risk of adverse fetal or pregnancy outcome (Coyle et al 2003). Conclusion Since the initial pilot trial of GA published in 1987, numerous clinical trials have consistently established its safety and efficacy as a first-line treatment of RRMS. Its role in reducing clinical activity of disease has also been supported by parallel MRI data. Laboratory and clinical studies have also helped to define its potential mechanisms of action, including a potentially unique mechanism of neuroprotection. Results of ongoing clinical trials may define its role in combination therapy as well as its efficacy in comparison with other established therapies. Future studies may also help to define other potential clinical applications of GA in the treatment of MS and other autoimmune disorders. Disclosures SAR is currently doing clinical trials (funded by research grants) with Teva (makers of glatiramer acetate), Genentech, Biogen, and Berlex. He has been a consultant to and has received honoraria from Teva, Berlex, Genentech, Biogen, and Serono. EK and JM have no conflicts of interest to disclose. 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, 31:433–8. Aharoni R, Kayhan B, Eilam R, et al. 2003. Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ. Proc Natl Acad Sci U S A, 100:14157–62. Azoulay D, Vachapova V, Shihman B, et al. 2005. Lower brain-derived neurotrophic factor in serum of relapsing-remitting MS: Reversal by glatiramer acetate. J Neuroimmunol, 167: 215–18. Bakshi R, Hutton GJ, Miller JR, et al. 2004. The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis. Neurology, 63:S3–11. Barde YA. 1997. Help from within for damaged axons. Nature, 385:391–3. Bernard CCA, Mandel TE, MacKay IR. 1992. Experimental models of human autoimmune disease:overview and prototypes. The Autoimmune Diseases II, 47–106. Bornstein MB, Miller AI, Slagle S, et al. 1987. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med, 317:408–14. Bornstein MB, Miller AI, Slagle S. 1991. A placebo controlled, double blinded, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Neurology, 41:533–9. 288 Bornstein MB, Miller AI, Teitelbaum D, et al. 1982. Multiple sclerosis: trial of a synthetic polypeptide. Ann Neurol, 11:317–19. Boneschi FM Rovaris M, Johnson KP, et al. 2003. Effects of glatiramer acetate on relapse rate and accumulated disability in multiple sclerosis: meta-analysis of three double-blinded, randomized, placebo-controlled clinical trials. Mult Scler, 9:349–55. Brenner T, Arnon R, Sela M, et al. 2001. Humoral and cellular immune responses to Copolymer I in MS patients treated with Copaxone. J Neuroimmunol, 115:152–60. Carra A, Onaha P, Sinay V, et al. 2003. A retrospective observational study comparing the four available immunomodulating treatments for RRMS. Eur J Neurol, 10:671–6. Chen M, Gran B, Costell K, et al. 2001. Glatiramer acetate induces a TH2- biased response and crossreactivity with myelin basic protein in patients with MS. Mult Scler, 7:209–19. Comi G, Filippi M, Wolinsky JS; the European/Canadian GA study group. 2001. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of GA on MRI-measured activity and burden in patients with relapsing multiple sclerosis. Ann Neurol, 49:290–7 . Coyle PK, Johnson KP, Pardo L, et al. 2003. Pregnancy outcomes in patients with multiple sclerosis treated with glatiramer acetate (Copaxone) [poster]. Proceedings of the 19th Annual Meeting of the European Committee for Treatment and Research in Multiple Scleroris (ECTRIMS). Milan, Italy. Poster 268 Dhib-Jalbut S. 2002. Mechanism of action of interferons and glatiramer acetate in multiple sclerosis. Neurology, 58(Suppl 4):S3–9. Duda PW, Schmied, Cook SL, et al. 2000. Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune response in patients with multiple sclerosis. J Clin Invest, 105:967–76. Farina C, Vargas V, Heydari N, et al. 2002. Treatment with glatiramer acetate induces specific IgG4 antibodies in multiple sclerosis patients. J Neuroimmunol, 123:188–92. Filippi M, Rovaris M, Rocca MA, et al. 2001. Glatiramer Acetate reduces the proportion of new MS lesions evolving into “black holes”. Neurology, 57:731–3. Fletcher S, Kott E, Steiner-Birmanns B, et al. 2002. Copolymer 1 in relapsing forms of MS: open multicenter study of alternate day administration. Clin Neuropharmacol, 25:11–15. Ford CC, Johnson KP, Lisak RP, et al, The Copaxone Study Group. 2006. A prospective open-label study of glatiramer acetate:over a decade of continuous use in multiple sclerosis patients. Mult Scler, 12:309–20. Ge Y, Grossman RI, Udupa JK, et al. 2000. Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS:Quantitative MR assessment. Neurology, 54:813. Gravel C, Gotz R, Lorrain A, Sendtner M. 1997. Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons. Nat Med, 3:765–70. Haas J. 2003. Onset of clinical benefit of glatiramer acetate in 255 patients with RRMS. Proceedings of the 55th Annual Meeting of the American Academy of Neurology. Honolulu, USA. p 06.105. Johnson KP, Brooks BR, Cohen JA, et al. 1995. Copolymer I reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled. The Copolymer I Multiple Sclerosis Study Group. Neurology, 45:1268–76. Kerschensteiner M, Stadelmann C, Dechang G, et al. 2003. Neurotrophic cross-talk between the nervous and immune systems: implications for neurological diseases. Ann Neurol, 53:292–304. Khan OH, Tselis AC, Kamholz JA, et al. 2001. A prospective, open label treatment trial to compare the effects of IFNβ-1a, IFNβ-1b, and glatiramer acetate on the relapse rate in RRMS: results after 18 months of therapy. Mult Scler, 7:349–53.Lewin GR, BardeYA. 1996. Physiology of the neurotrophins. Annu Rev Neurosci, 19:289–317. Lobel E, Riven-Kreitman R, Amselem A, et al. 1996. Copolymer-I. Drugs Future, 21:131–4. international Journal of Nanomedicine 2006:1(3)