Comi G, Moiola L
Neurophysiology Department, San Raffaele Scientific Institute, Milan, Italy.
Baillieres Clin Neurol. 1997 Oct;6(3):495-509.
Copolymer 1 (Cop-1) is a mixture of synthetic polypeptides composed of four amino acids. Cop-1 was very effective in suppression of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). Two principal mechanisms have been proposed to explain the suppressive activity of Cop-1 in EAE and in multiple sclerosis (MS): the induction of antigen-specific suppressor T cells and the interference with T-cell activation by competition with myelin antigens in binding to the major histocompatibility complex class II molecules. Clinical trials with Cop-1 have demonstrated that Cop-1 positively alters the course of relapsing-remitting multiple sclerosis (MS) by both reducing the relapse rate and slowing the progression of disability. In a 2-year multi-centre, randomized, double-blind, placebo-controlled trial of 251 patients, Cop-1 was shown to reduce relapses by an average of 29% when compared with placebo. A preliminary study on patients with relapsing-remitting MS treated with Cop-1 showed a reduced number of new enhancing lesions on MRI as well as a reduced accumulation of lesion load during Cop-1 treatment. Antibodies to copolymer-1, which are found during Cop-1 treatment, do not interfere with its clinical effects. The side effects of Cop-1 are minimal and acceptable. In vitro and in vivo animal studies have shown a very good safety profile of Cop-1 which is devoid of teratogenic or mutagenic effects. Cop-1 joins interferon beta as a good candidate for treatment of relapsing-remitting MS.
共聚体1(Cop-1)是一种由四种氨基酸组成的合成多肽混合物。Cop-1在抑制实验性自身免疫性脑脊髓炎(EAE)方面非常有效,EAE是多发性硬化症(MS)的动物模型。已提出两种主要机制来解释Cop-1在EAE和多发性硬化症(MS)中的抑制活性:诱导抗原特异性抑制性T细胞以及通过与髓鞘抗原竞争结合主要组织相容性复合体II类分子来干扰T细胞活化。Cop-1的临床试验表明,Cop-1通过降低复发率和减缓残疾进展,积极改变复发缓解型多发性硬化症(MS)的病程。在一项针对251名患者的为期2年的多中心、随机、双盲、安慰剂对照试验中,与安慰剂相比,Cop-1显示平均可将复发率降低29%。一项对接受Cop-1治疗的复发缓解型MS患者的初步研究表明,MRI上新的强化病灶数量减少,且在Cop-1治疗期间病灶负荷的积累也减少。在Cop-1治疗期间发现的针对共聚体-1的抗体并不干扰其临床效果。Cop-1的副作用极小且可接受。体外和体内动物研究表明Cop-1具有非常好的安全性,没有致畸或致突变作用。Cop-1与干扰素β一样,是治疗复发缓解型MS的良好候选药物。