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  • Title: Proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDL lowering in the contemporary management of dyslipidemia.
    Author: Switzer MP, Nwosu AC, Juan ZS, Mukherjee D.
    Journal: Cardiovasc Hematol Agents Med Chem; 2013 Dec; 11(4):281-8. PubMed ID: 24164109.
    Abstract:
    PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) protein plays an important role in LDL cholesterol (LDL-C) metabolism, due to its role in the degradation of the LDL receptor. Preliminary clinical data of PCSK9 inhibition are quite promising and indicate that PCSK9 inhibition may be a novel strategy for the treatment of dyslipidemia particularly for those with refractory hypercholesterolemia, statin intolerance, or an elevated lipoprotein (a) level and associated cardiovascular diseases. Furthermore, development of PCSK9 inhibitor is an excellent example of "bench to bedside" concept where discovery of a genetic mutation was translated into a novel therapy to address unmet clinical needs. Although several approaches have been attempted to inhibit PCSK9 activity including small molecules, gene silencing and inhibitory antibodies, the most promising approach appears to be the use of monoclonal antibodies with a 50 -70% LDL cholesterol reduction on top of maximal doses of statins. In this article, we review the pharmacology of PCSK9 and summarize findings from key clinical studies using PCSK9 inhibitors.
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