抗补体药物 LY课件

1、Complement-targeted therapeuticsActivation of the complement systemThe complement system in innate and adaptive immunityOne of the most fascinating aspects of complement is the sophisticatedregulation mechanism that allows a rapid reaction to pathogenic intruderswhile protecting host cells from its

2、destructive potential.The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response.However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological（病理） conditions. Modulation of t

3、he complement system has been recognized as a promising strategy in drug discovery, and a large number of therapeutic modalities（方式）have been developed. BackgroundImmune surveillance functions of complementComplements involvement in disease局部中风Alzheimers 病(老年痴呆)老年性黄斑变性症哮喘心肌梗塞非典型溶血尿毒综合征Crohns 病类风湿性关节

4、炎（RA）Current complement therapeutics焦点问题：过度活化或调节不足治疗策略：抑制补体活化，调节补体活性面临困难： 补体系统作用的多面性及致病机制的复杂性 新药成药性（druggability） 靶点的确定及药物作用的特异性（适应症）A.丝氨酸蛋白酶抑制剂（C1r,C1s,C2a,MASP-1,MASP-2,factor D, factor B, factor I） 目前只有一种C1抑制剂浓缩剂（C1-INH）上市，用于治疗遗传性血管性水肿-C1-INH减少B.可溶性补体调节蛋白（如sCR1）C.治疗性抗体：EculizumabD.补体成分的抑制剂（如短肽，核酸

5、，合成物等）（compstatin,治疗老年性黄斑变性症）E.过敏毒素受体拮抗剂（如C5a受体）其他（如重组人MBL的替代疗法）研究策略与方向 抗补体治疗是一个令人兴奋的免疫治疗学前沿领域。不久的将来，抑制补体将成为一种公认的临床疗法。理想的补体抑制治疗制剂应该是：分子小、无抗原性、特异、高效、体内作用时间长、价廉。Steep terrain: To move a therapy from the research lab to the doctors office requires a huge investment in clinical trials, which are growing

6、 more costly and more complex every year. Thank you!参考文献 1.Complement-targeted therapeutics. Nature Biotechnology. 2007, 25:1265-75.2. Complement and its role in innate and adaptive immune responses. Cell Research. 2010, 20:34-50.3.Complement:a key system for immune surveillance and homeostasis. Nature Immunology. 2010,11:785-97.4.陈政良教授（南方医科大学，免疫教研室）的教学幻灯美国FDA于2007年3月16日批准了Soliris (eculizumab)用于治疗用于治疗阵发性夜间血尿症（PNH），这是FDA批准的首个用于治疗该症的药物，该药由Alexion Pharmaceuticals公司开发。PNH为一种罕见的威胁生命的溶血性贫血，平均患者年龄为30岁。可导致残疾或早期死亡。 PNH患者缺少一种保护红细胞不被破坏的特殊蛋白质，红细胞由于受到补体