PCSK9 单克隆抗体作用机制与临床研究进展

前蛋白转化酶枯草溶菌素9(PCSK9)是前蛋白转化酶家族成员之一,它通过与肝细胞表面低密度脂蛋白受体(LDLR)结合,使体内低密度脂蛋白水平升高,引发高血脂。PSCK9抑制剂可以达到降低血脂的临床效果并已经成为重要的减少冠心病发病率的药物靶点。尤其是单克隆抗体药物,作为目前唯一的具有降脂功能的单克隆抗体,在临床试验上的表现对于家族遗传性高血脂的治疗及冠心病的防治都具有重要意义。本文将主要对PCSK9的作用机制及其单克隆抗体的研发现状、临床试验进展进行总结,旨在对降脂单抗药物研发与临床应用作为参考。

Clinical Research of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9)Monoclonal Antibodies

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a member of subtilisin-like proprotein convertase family. Byinteracting with low density lipoprotein receptor (LDLR) on the surface of hepatocyte, PCSK9 plays an important role in elevating thelevel of low density lipoprotein (LDL) and finally leading to hyperlipidemia. The PCSK9-inhibitor is now being an important and totallynew therapeutic target to reduce the incidence of coronary heart disease through its function of lipid lowering. Especially, as the onlytheraputic antibody-drug with lipid-lowering function, the lipid depressing effect of monoclonal antibodies has crucial meaning for thetherapy of familial transmissibility hyperlipidemia and the prevention of coronary heart disease. In this article, the mechanism of PCSK9,the research and development status, the safety and clinical efficacy of PCSK9 monoclonal antibodies will be briefly reviewed, with thepurpose to provide important reference for research and development of monoclonal antibodies to PCSK9.