B细胞耐受原阿贝莫司钠的研究现状及启示

Research progress of B cell tolerangen abetimus sodium and its revelation

阿贝莫司钠(abetimus sodium,LJP-394)是美国La Jolla制药公司历时20多年研究开发的拟用于治疗系统性红斑狼疮的新药。阿贝莫司钠属于B细胞耐受原,可与B细胞抗dsDNA抗体交联而诱导B细胞产生免疫耐受。在Ⅲ期临床试验中,阿贝莫司钠能降低部分狼疮性肾炎患者抗dsDNA抗体水平,但对肾炎复发无明显的保护作用。因此,2009年La Jolla制药公司宣布终止了阿贝莫司钠的临床试验。本文对就阿贝莫司钠的作用特点和研究脉络作一综述,为研究开发治疗系统性红斑狼疮的新药提供借鉴。

Abetimus sodium ( LJP-394,Riquent) is an investigational agent specifically designed to decrease anti-dsDNA antibody levels. It has been under development for the prevention of nephritic flares in patients with systemic lupus erythematosus since the early 1990s. In 2009,La Jolla Pharmaceutical Company announced that for lack of efficacy the development of abetimus sodium would be suspended. This paper reviews the principal aspects of chemistry,pharmacokinetics,efficacy and safety of abetimus sodium,and analyzes the studies on animal models and clinical studies conducted in the last years.