Journal
CURRENT OPINION IN LIPIDOLOGY
Volume 24, Issue 4, Pages 307-312Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOL.0b013e328361f62d
Keywords
cardiovascular disease; clinical trial; LDL receptor; monoclonal antibodies; PCSK9
Funding
- National Health & Medical Research Council of Australia [101867]
- Agence Nationale de la Recherche
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Purpose of review In the past 10 years, the LDL receptor inhibitor proprotein convertase subtilisin kexin type 9 (PCSK9) has emerged as a validated target for lowering plasma LDL cholesterol levels. Here we review the most recent reports on PCSK9 out of a total of 500 publications published in print or online before March 2013 and indexed on PubMed. Recent findings All published in 2012, phase I and II clinical trials demonstrate that fully human monoclonal antibodies targeting PCSK9 dramatically reduce LDL-C and enable patients to reach their target goals, without severe or serious safety issues. Summary This review summarizes the discovery of PCSK9, its original mode of action as a secreted inhibitor of the LDL receptor, as well as its genetic regulation by statins. We then focus on the major results from the 2012 phase I and II PCSK9 inhibitor clinical trials. We also review the recent in-vivo studies demonstrating the potential cardiovascular benefits of long-term PCSK9 inhibition and discuss its potential side-effects.
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