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.
References
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).
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).
Qian, Y. W. et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J. Lipid Res. 48, 1488–1498 (2007).
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).
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).
Lambert, G., Sjouke, B., Choque, B., Kastelein, J. J. & Hovingh, G. K. The PCSK9 decade. J. Lipid Res. 53, 2515–2524 (2012).
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).
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).
Kathiresan, S. Lp(a) lipoprotein redux—from curious molecule to causal risk factor. N. Engl. J. Med. 361, 2573–2574 (2009).
Nordestgaard, B. G. et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur. Heart J. 31, 2844–2853 (2010).
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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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DOI: https://doi.org/10.1038/nrcardio.2013.139
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