Dhib-Jalbut Suhayl
Department of Veterans Affairs, Baltimore, MD, USA.
Pharmacol Ther. 2003 May;98(2):245-55. doi: 10.1016/s0163-7258(03)00036-6.
Glatiramer acetate (GA) (Copaxone(R)) is a worldwide-approved drug for the treatment of relapsing multiple sclerosis (MS), an autoimmune disease of the CNS. The drug is a synthetic copolymer with an amino acid composition based on the structure of myelin basic protein, one of the autoantigens implicated in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE). Developed initially as a "tool" to study EAE, the drug unexpectedly inhibited disease and was subsequently developed for the treatment of MS. The drug has been shown in controlled clinical trials to significantly reduce relapse rate and progression of disability in MS with long-term efficacy, remarkable safety, and tolerability. Efficacy as measured by magnetic resonance imaging parallels its clinical benefits as manifested by a reduction in gadolinium-enhancing lesions and brain atrophy. The mechanism of action of the drug in humans is believed to involve the induction of glatiramer-reactive regulatory cells, including CD4+ and CD8+ T-cells. Glatiramer-reactive Th2 cells are believed to enter the brain and, through cross-reactivity with myelin antigens, produce bystander suppression, antiinflammatory effects, and neuroprotection.
醋酸格拉替雷（GA）（考帕松®）是一种全球获批用于治疗复发型多发性硬化症（MS）的药物，MS是一种中枢神经系统自身免疫性疾病。该药物是一种合成共聚物，其氨基酸组成基于髓鞘碱性蛋白的结构，髓鞘碱性蛋白是与MS和实验性自身免疫性脑脊髓炎（EAE）发病机制相关的自身抗原之一。该药物最初作为研究EAE的“工具”开发，却意外地抑制了疾病，随后被开发用于治疗MS。在对照临床试验中已表明，该药物可显著降低MS的复发率和残疾进展，具有长期疗效、显著的安全性和耐受性。通过磁共振成像测量的疗效与其临床益处相当，表现为钆增强病变和脑萎缩减少。该药物在人体中的作用机制被认为涉及诱导格拉替雷反应性调节细胞，包括CD4+和CD8+ T细胞。格拉替雷反应性Th2细胞被认为进入大脑，并通过与髓鞘抗原的交叉反应，产生旁观者抑制、抗炎作用和神经保护作用。
