Centre for Amyloidosis and Acute Phase Proteins and the National Amyloidosis Centre, University College London Medical School, London, UK.
Br J Haematol. 2010 Mar;148(5):760-7. doi: 10.1111/j.1365-2141.2009.08036.x. Epub 2010 Jan 8.
Serum amyloid P component (SAP) is a universal constituent of amyloid deposits and contributes to their formation and/or persistence. We therefore developed CPHPC ((R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexa-noyl]pyrrolidine-2 carboxylic acid), a novel bis(D-proline) drug, to specifically target SAP and report here a first, exploratory, open label proof of principle study in systemic amyloidosis. CPHPC produced sustained, >95% depletion of circulating SAP in all patients and c. 90% reduction in the SAP content of the two amyloidotic organs that became available. There were no significant adverse effects of either SAP depletion or CPHPC itself. No accumulation of amyloid was demonstrable by SAP scintigraphy in any patient on the drug. In hereditary fibrinogen amyloidosis, which is inexorably progressive, proteinuria was reduced in four of five patients receiving CPHPC and renal survival was prolonged compared to a historical control group. These promising clinical observations merit further study.
血清淀粉样蛋白 P 成分（SAP）是淀粉样沉积物的普遍组成部分，有助于其形成和/或持续存在。因此，我们开发了 CPHPC（（R）-1-[6-（R）-2-羧基-吡咯烷-1-基]-6-氧代-己酰基]吡咯烷-2 羧酸），一种新型双（D-脯氨酸）药物，专门针对 SAP，并在此报告全身性淀粉样变性的首次探索性、开放性原理研究。CPHPC 使所有患者的循环 SAP 持续、>95%耗尽，两种淀粉样变器官的 SAP 含量降低约 90%。SAP 耗竭或 CPHPC 本身均无明显不良反应。在任何接受药物治疗的患者中，SAP 闪烁扫描均未显示任何部位的淀粉样物质蓄积。在不可避免地进行性遗传纤维蛋白原淀粉样变性中，接受 CPHPC 治疗的五名患者中有四名蛋白尿减少，与历史对照组相比，肾功能延长。这些有希望的临床观察值得进一步研究。
