oa The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research

References

1. Hall J, Dib N. The path from pre-clinical research to FDA approval. J Cardiovasc Transl Res. 2008; 1:2:93–94.
   [Google Scholar]
2. Stamler J. The problem of elevated blood cholesterol. Am J Public Health Nations Health. 1960; 50:3 Pt 2:14–19.
   [Google Scholar]
3. Kannel WB, Dawber TR, Friedman GD, Glennon WE, McNamara PM. Risk factors in coronary heart disease. An evaluation of several serum lipids as predictors of coronary heart disease; the framingham study. Ann Intern Med. 1964; 61::888–899.
   [Google Scholar]
4. Kannel WB, Castelli WP, McNamara PM. Serum lipid fractions and risk of coronary heart disease. The Framingham study. Minn Med. 1969; 52::1225–1230.
   [Google Scholar]
5. Hovingh GK, Davidson MH, Kastelein JJP, O'Connor AM. Diagnosis and treatment of familial hypercholesterolaemia. Eur Heart J. 2013; 34:13:962–971.
   [Google Scholar]
6. Ibrahim M, El-Hamamsy I, Barbir M, Yacoub MH. Translational lessons from a case of combined heart and liver transplantation for familial hypercholesterolemia 20 years post-operatively. J Cardiovasc Transl Res. 2012; 5:3:351–358.
   [Google Scholar]
7. Goldstein JL, Brown MS. Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proc Natl Acad Sci U S A. 1973; 70::2804–2808.
   [Google Scholar]
8. Goldstein JL, Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974; 249::5153–5162.
   [Google Scholar]
9. Abifadel M, Varret M, Rabés JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003; 34::154–156.
   [Google Scholar]
10. Leren TP. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin Genet. 2004; 65::419–422.
    [Google Scholar]
11. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005; 37::161–165.
    [Google Scholar]
12. Chan JC, Piper DE, Cao Q, Liu D, King C, Wang W, Tang J, Liu Q, Higbee J, Xia Z, Di Y, Shetterly S, Arimura Z, Salomonis H, Romanow WG, Thibault ST, Zhang R, Cao P, Yang XP, Yu T, Lu M, Retter MW, Kwon G, Henne K, Pan O, Tsai MM, Fuchslocher B, Yang E, Zhou L, Lee KJ, Daris M, Sheng J, Wang Y, Shen WD, Yeh WC, Emery M, Walker NP, Shan B, Schwarz M, Jackson SM. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci U S A. 2009; 106::9820–9825.
    [Google Scholar]
13. Ni YG, Di Marco S, Condra JH, Peterson LB, Wang W, Wang F, Pandit S, Hammond HA, Rosa R, Cummings RT, Wood DD, Liu X, Bottomley MJ, Shen X, Cubbon RM, Wang SP, Johns DG, Volpari C, Hamuro L, Chin J, Huang L, Zhao JZ, Vitelli S, Haytko P, Wisniewski D, Mitnaul LJ, Sparrow CP, Hubbard B, Carfí A, Sitlani A. A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo. J Lipid Res. 2011; 52::78–86.
    [Google Scholar]
14. Liang H, Chaparro-Riggers J, Strop P, Geng T, Sutton JE, Tsai D, Bai L, Abdiche Y, Dilley J, Yu J, Wu S, Chin SM, Lee NA, Rossi A, Lin JC, Rajpal A, Pons J, Shelton DL. Proprotein convertase substilisin/kexin type 9 antagonism reduces low-density lipoprotein cholesterol in statin-treated hypercholesterolemic nonhuman primates. J Pharmacol Exp Ther. 2012; 340::228–236.
    [Google Scholar]
15. Frank-Kamenetsky M, Grefhorst A, Anderson NN, Racie TS, Bramlage B, Akinc A, Butler D, Charisse K, Dorkin R, Fan Y, Gamba-Vitalo C, Hadwiger P, Jayaraman M, John M, Jayaprakash KN, Maier M, Nechev L, Rajeev KG, Read T, Röhl I, Soutschek J, Tan P, Wong J, Wang G, Zimmermann T, de Fougerolles A, Vornlocher HP, Langer R, Anderson DG, Manoharan M, Koteliansky V, Horton JD, Fitzgerald K. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci U S A. 2008; 105::11915–11920.
    [Google Scholar]
16. Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, Hutabarat RM, Clausen VA, Karsten V, Cehelsky J, Nochur SV, Kotelianski V, Vaishnaw AK, Gollob JA, Simon A. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet. 2014; 383::60–68, doi:10.1016/S0140-6736(13)61914-5. Published Online: 03 October 2013.
    [Google Scholar]
17. Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, Wasserman SM, Stein EA. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA. 2012; 308::2497–2506.
    [Google Scholar]
18. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, Lisbon E, Gutierrez M, Webb C, Wu R, Du Y, Kranz T, Gasparino E, Swergold GD. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012; 366::1108–1118.
    [Google Scholar]
19. Koren MJ, Giugliano RP, Raal FJ, Sullivan D, Bolognese M, Langslet G, Civeira F, Somaratne R, Nelson P, Liu T, Scott R, Wasserman SM, Sabatine MS, for the OSLER Investigators . Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-Week results from the open-label study of long-term evaluation against LDL-C (OSLER) Randomized Trial. Circulation., CIRCULATIONAHA.113.007012–(2013). doi:10.1161/CIRCULATIONAHA.113.007012 .
    [Google Scholar]
20. Shan L, Pang L, Zhang R, Murgolo NJ, Lan H, Hedrick JA. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun. 2008; 375::69–73.
    [Google Scholar]
21. Melone M, Wilsie L, Palyha O, Strack A, Rashid S. Discovery of a new role of human resistin in hepatocyte low-density lipoprotein receptor suppression mediated in part by proprotein convertase subtilisin/kexin type 9. J Am Coll Cardiol. 2012; 59:19:1697–1705.
    [Google Scholar]
22. Weikert C, Westphal S, Berger K, Dierkes J, Möhlig M, Spranger J, Rimm EB, Willich SN, Boeing H, Pischon T. Plasma resistin levels and risk of myocardial infarction and ischemic stroke. J Clin Endocrinol Metab. 2008; 93:7:2647–2653.
    [Google Scholar]
23. Hassan M, Latif N, Yacoub M. Adipose tissue: friend or foe? Nat Rev Cardiol. 2012; 9::689–702.
    [Google Scholar]
24. Sahebkar A. Beyond anti-PCSK9 therapies: the potential role of resistin inhibitors. Nat Rev Cardiol. 2014; 11:1:12.
    [Google Scholar]
25. Goldstein JL. Juxtapositions in trafalgar square: tip-offs to creativity in art and science. Nat Med. 2013; 19::1222–1226.
    [Google Scholar]