University of Maryland Baltimore, Baltimore, Maryland 21201, USA.
Expert Opin Drug Metab Toxicol. 2010 May;6(5):643-60. doi: 10.1517/17425251003752715.
MS is a chronic progressive inflammatory and neurodegenerative disease associated with autoimmune dysregulation. Glatiramer acetate (GA), a complex polypeptides mixture and first member of the glatiramoid class, is a first-line therapy for relapsing MS. New glatiramoids are under development.
Studies from a PubMed search with terms 'glatiramer' and 'glatiramoid' were evaluated, focussing on studies conducted between 2007 and 2010.
We review newly discovered GA effects on innate and acquired immunity and results of recent clinical studies. GA delays conversion from a clinically isolated syndrome to definite MS and has clinical benefits comparable to those of IFN-beta drugs, but is more cost-effective and improves quality of life. Preclinical studies of protiramer, a higher molecular mass glatiramoid, showed unexpected toxicity in animals, resulting in discontinuation of drug development.
GA is a cost-effective, safe and efficacious MS treatment with pleiotropic immunomodulation activity, is best prescribed early and may safely enhance outcomes when used with other immunomodulators. Protiramer experience indicates the potential for unexpected toxicity associated with new glatiramoids. The safety, efficacy and immunogenicity of new glatiramoids must be evaluated thoroughly.
多发性硬化症是一种慢性进行性炎症和神经退行性疾病,与自身免疫失调有关。醋酸格拉替雷(GA),一种复杂的多肽混合物,是第一个获批的用于治疗多发性硬化症的疾病调节药物。新的疾病调节药物正在开发中。
评估了使用术语“glatiramer”和“glatiramoid”进行 PubMed 搜索的研究,重点关注 2007 年至 2010 年期间进行的研究。
我们回顾了新发现的 GA 对固有和获得性免疫的影响,以及最近临床试验的结果。GA 可延迟从临床孤立综合征到明确多发性硬化症的转化,并且具有与 IFN-β药物相当的临床获益,但成本效益更高,可提高生活质量。较高分子量的 glatiramoid protiramer 的临床前研究在动物中显示出意外的毒性,导致药物开发停止。
GA 是一种具有成本效益、安全且有效的多发性硬化症治疗药物,具有广泛的免疫调节活性,最好在早期使用,与其他免疫调节剂联合使用时可能会更安全地改善治疗结果。protiramer 的经验表明,新型 glatiramoid 可能存在意外毒性。必须全面评估新型 glatiramoid 的安全性、疗效和免疫原性。