PCSK9 inhibitors: The next frontier in low-density lipoprotein lowering

Ishwarlal Jialal, Shailendra B. Patel

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The discovery and elucidation of the role of the low-density lipoprotein receptor (LDL-R) in familial hypercholesterolemia (FH) ushered in the statin group of drugs. These drugs, in addition to lowering low-density lipoprotein cholesterol (LDL-C), result in a significant reduction in cardiovascular events (CVE) and mortality. Recently, a gain-of-function mutation in another protein, proprotein convertase subtilisin/kexin type 9 (PCSK9), was reported to result in a FH phenotype by promoting degradation of the LDL-R. More importantly, loss-of-function mutations in the same gene resulted in low LDL-C and a reduction in CVE, making this an enticing target for drug development. Numerous strategies have been developed to target PCSK9, the most successful being monoclonal antibodies (mAbs) that bind PCSK9. These mAbs have been shown to reduce LDL-C around 50% as either monotherapy with diet or in combination with statin therapy. In this short perspective, we discuss the biochemistry and biology of PCSK9 in relation to lipid metabolism and the promising studies in humans demonstrating a substantial reduction in LDL-C with relative good short-term safety of PCSK9 mAbs.

Original languageEnglish (US)
Pages (from-to)99-101
Number of pages3
JournalMetabolic Syndrome and Related Disorders
Issue number3
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine


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