Emerging low-density lipoprotein therapies: Targeting PCSK9 for low-density lipoprotein reduction

Journal of Clinical Lipidology

Volumn 7, Issue 3 SUPPL., 2013, Pages

  Davidson, Michael H ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

Familial hypercholesterolemia; Low density lipoprotein cholesterol; Monoclonal antibody; Proprotein convertase subtilisin kexin type 9

Indexed keywords

ALIROCUMAB; AMG 145; APOLIPOPROTEIN B; ATORVASTATIN; BILE ACID SEQUESTRANT; CELL PROTEIN; CLATHRIN; EZETIMIBE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN RECEPTOR; MONOCLONAL ANTIBODY; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG;

ARTICLE; DOSE RESPONSE; DRUG EFFICACY; DRUG SAFETY; FAMILIAL HYPERCHOLESTEROLEMIA; GAIN OF FUNCTION MUTATION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTRANSAMINASEMIA; INJECTION SITE REACTION; LOSS OF FUNCTION MUTATION; MYALGIA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN TARGETING; SINGLE DRUG DOSE; WEAKNESS;

ANTIBODIES, MONOCLONAL; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; LIPOPROTEINS, LDL; PROPROTEIN CONVERTASES; SERINE ENDOPEPTIDASES;

EID: 84877267055     PISSN: 19332874     EISSN: 18764789     Source Type: Journal    
DOI: 10.1016/j.jacl.2013.03.004     Document Type: Article

References (27)

1. C.J. Glueck, P. Gartside, R.W. Fallat, J. Sielski, and P.M. Steiner Longevity syndromes: familial hypobeta and familial hyperalpha lipoproteinemia J Lab Clin Med 88 1976 941 957
2. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Third report of the National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report Circulation 106 2002 3143 3421
3. J.C. Cohen, E. Boerwinkle, T.H. Mosley Jr., and H.H. Hobbs Sequence variations in PCSK9, low LDL, and protection against coronary heart disease N Engl J Med 354 2006 1264 1272
4. P. Pauciullo, M. Gentile, and G. Marotta Small dense low-density lipoprotein in familial combined hyperlipidemia: independent of metabolic syndrome and related to history of cardiovascular events Atherosclerosis 203 2009 320 324
5. J. Cohen, A. Pertsemlidis, and I.K. Kotowski Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9 Nat Genet 37 2005 161 165
6. A.S. Peterson, L.G. Fong, and S.G. Young PCSK9 function and physiology J Lipid Res 49 2008 1595 1599
7. A.S. Wierzbicki, T.C. Hardman, and A. Viljoen Inhibition of pro-protein convertase subtilisin kexin 9 (PCSK-9) as a treatment for hyperlipidaemia Expert Opin Investig Drugs 21 2012 667 676
8. M.S. Brown, and J.L. Goldstein Receptor-mediated endocytosis: insights from the lipoprotein receptor system Proc Natl Acad Sci USA 76 1979 3330 3337
9. Y.W. Qian, R.J. Schmidt, and Y. Zhang Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis J Lipid Res 48 2007 1488 1498
10. D. Steinberg, and J.L. Witztum Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels Proc Natl Acad Sci U S A 106 2009 9546 9547
11. J.L. Goldstein, and M.S. Brown The LDL receptor Arterioscler Thromb Vasc Biol 29 2009 431 438
12. D.W. Zhang, T.A. Lagace, and R. Garuti Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation J Biol Chem 282 2007 18602 18612
13. J.D. Horton, J.C. Cohen, and H.H. Hobbs PCSK9: a convertase that coordinates LDL catabolism J Lipid Res 50 Suppl 2009 S172 S177
14. C. Dubuc, A. Chamberland, and H. Wassef Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia Arterioscler Thromb Vasc Biol 24 2004 1454 1459
15. T. Fasano, X.M. Sun, D.D. Patel, and A.K. Soutar Degradation of LDLR protein mediated by 'gain of function' PCSK9 mutants in normal and ARH cells Atherosclerosis 203 2009 166 171
16. G. Lambert, B. Sjouke, B. Choque, J.J. Kastelein, and G.K. Hovingh The PCSK9 decade J Lipid Res 53 2012 2515 2524
17. E.A. Stein, S. Mellis, and G.D. Yancopoulos Effect of a monoclonal antibody to PCSK9 on LDL cholesterol N Engl J Med 366 2012 1108 1118
18. J.M. McKenney, M.J. Koren, and D.J. Kereiakes Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy J Am Coll Cardiol 59 2012 2344 2353
19. E.M. Roth, J.M. McKenney, C. Hanotin, G. Asset, and E.A. Stein Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia N Engl J Med 367 2012 1891 1900
20. C.S. Dias, A.J. Shaywitz, and S.M. Wasserman Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins J Am Coll Cardiol 60 2012 1888 1898
21. F. Raal, R. Scott, and R. Somaratne Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial Circulation 126 2012 2408 2417
22. D. Sullivan, A.G. Olsson, and R. Scott Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial JAMA 308 2012 2497 2506
23. M.J. Koren, R. Scott, and J.B. Kim Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study Lancet 380 2012 1995 2006
24. R.P. Giugliano, N.R. Desai, and P. Kohli LAPLACE-TIMI 57 Investigators 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 2012 2007 2017
25. J. Chaparro-Riggers, H. Liang, and R.M. DeVay Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9 J Biol Chem 287 2012 11090 11097
26. B. Gumbiner, C. Udata, and T. Joh The effects of multiple dose administration of RN316 (PF-04950615), a humanized IgG2Δa monoclonal antibody binding proprotein convertase subtilisin kexin type 9, in hypercholesterolemia subjects Circulation 126 2012 A13524
27. A.J. Lusis, and P. Pajukanta A treasure trove for lipoprotein biology Nat Genet 40 2008 129 130