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Dyslipidaemia

PCSK9 antibodies: a dividend of the genomics revolution

Nature Reviews Cardiology volume 10, pages 618–619 (2013)Cite this article

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PCSK9 antibodies effectively lower the LDL-cholesterol level and, therefore, address an unmet clinical need in patients with either refractory hypercholesterolaemia, statin intolerance, or an elevated lipoprotein(a) level. On the basis of ongoing clinical outcome trials, these agents might reset the target LDL-cholesterol level to <50 mg/dl.

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Figure 1: Mechanism of PCSK9 inhibition with monoclonal antibodies.

References

  1. Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr & Hobbs, H. H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006).

    Article  CAS  Google Scholar 

  2. Cohen, J. et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat. Genet. 37, 161–165 (2005).

    Article  CAS  Google Scholar 

  3. Qian, Y. W. et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J. Lipid Res. 48, 1488–1498 (2007).

    Article  CAS  Google Scholar 

  4. Steinberg, D. & Witztum, J. L. Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels. Proc. Natl Acad. Sci. USA 106, 9546–9547 (2009).

    Article  CAS  Google Scholar 

  5. Fasano, T., Sun, X. M., Patel, D. D. & Soutar, A. K. Degradation of LDLR protein mediated by 'gain of function' PCSK9 mutants in normal and ARH cells. Atherosclerosis 203, 166–171 (2009).

    Article  CAS  Google Scholar 

  6. Lambert, G., Sjouke, B., Choque, B., Kastelein, J. J. & Hovingh, G. K. The PCSK9 decade. J. Lipid Res. 53, 2515–2524 (2012).

    Article  CAS  Google Scholar 

  7. Giugliano, R. P. et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 380, 2007–2017 (2012).

    Article  CAS  Google Scholar 

  8. Desai, N. R. et al. AMG 145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment With Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)–Thrombolysis in Myocardial Infarction (TIMI) 57 trial. Circulation 128, 962–969 (2013).

    Article  CAS  Google Scholar 

  9. Kathiresan, S. Lp(a) lipoprotein redux—from curious molecule to causal risk factor. N. Engl. J. Med. 361, 2573–2574 (2009).

    Article  CAS  Google Scholar 

  10. Nordestgaard, B. G. et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur. Heart J. 31, 2844–2853 (2010).

    Article  CAS  Google Scholar 

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  1. The University of Chicago Pritzker School of Medicine, 150 East Huron, Chicago, IL 60611, USA

    Michael H. Davidson

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  1. Michael H. Davidson
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Correspondence to Michael H. Davidson.

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Competing interests

M. H. Davidson declares that he is a consultant for Amgen and Sanofi-Aventis, which are developing PCSK9 monoclonal antibodies.

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Davidson, M. PCSK9 antibodies: a dividend of the genomics revolution. Nat Rev Cardiol 10, 618–619 (2013). https://doi.org/10.1038/nrcardio.2013.139

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