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  • Title: PCSK9 antibodies: A new class of lipid-lowering drugs.
    Author: Gouni-Berthold I.
    Journal: Atheroscler Suppl; 2015 May; 18():21-7. PubMed ID: 25936300.
    Abstract:
    The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to the lysosome for degradation. This results in decreased numbers of LDLR available on the cell surface to bind LDL particles and remove them from the circulation and a subsequent increase in circulating LDL-cholesterol (LDL-C) concentrations. Since the role PCSK9 plays in LDL-C metabolism has been discovered in 2003, there have been major efforts in finding efficient and safe methods to inhibit it. Amongst those, the PCSK9 antibodies are the furthest in development, with multiple phase III and cardiovascular endpoint trials already underway. These fully human monoclonal antibodies have been extensively studied in a wide range of subjects such as in those with statin intolerance, as add-on to statin therapy, as monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies have shown to be associated with a consistent robust additional decrease in LDL-C concentrations of around 50-70%. If the safety data from the ongoing phase III trials remain as reassuring as the data available till now, PCSK9 antibodies are going to offer a new, powerful therapeutic option to decrease LDL-C concentrations and hopefully cardiovascular risk.
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