Effects of an antisense oligonucleotide inhibitor of C-reactive protein synthesis on the endotoxin challenge response in healthy human male volunteers

Journal of the American Heart Association

Volumn 3, Issue 4, 2014, Pages

  Noveck, Robert ^a   Stroes, Erik S G ^b   Flaim, JoAnn D ^c   Baker, Brenda F ^c   Hughes, Steve ^c   Graham, Mark J ^c   Crooke, Rosanne M ^c   Ridker, Paul M ^d  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

^c ISIS PHARMACEUTICALS   (United States)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Acute phase response; Antisense inhibitor; C reactive protein; Endotoxin; Healthy volunteers

Indexed keywords

ANTIBIOTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; C REACTIVE PROTEIN; CAFFEINE; COMPLEMENT ACTIVATION BB; COMPLEMENT ACTIVATION C4; COMPLEMENT ACTIVATION C5A; COMPLEMENT COMPONENT C1; D DIMER; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ENDOTOXIN; FIBRINOGEN; HERBACEOUS AGENT; INTERLEUKIN 1BETA; INTERLEUKIN 6; ISIS 329993; LIPOPOLYSACCHARIDE BINDING PROTEIN; MONOCYTE CHEMOTACTIC PROTEIN 1; NON PRESCRIPTION DRUG; PARACETAMOL; PLACEBO; PROTHROMBIN; SERUM AMYLOID A; THROMBIN; THROMBIN ANTITHROMBIN COMPLEX; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VITAMIN; CCL2 PROTEIN, HUMAN; FIBRIN DEGRADATION PRODUCT; FIBRIN FRAGMENT D; IL6 PROTEIN, HUMAN; OLIGONUCLEOTIDE; PEPTIDE FRAGMENT; PROTHROMBIN FRAGMENT 1.2; TUMOR NECROSIS FACTOR;

ABDOMINAL PAIN; ACUTE PHASE RESPONSE; ADULT; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BLOOD CLOTTING TEST; CACAO; CARBONATED BEVERAGE; COFFEE; COHORT ANALYSIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DERMATITIS; DIET RESTRICTION; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG CONTRAINDICATION; DRUG SAFETY; DRUG TOLERABILITY; ECHOCARDIOGRAPHY; FIBRINOLYSIS; FOLLOW UP; GASTROENTERITIS; HEADACHE; HEMATOLOGICAL PARAMETERS; HUMAN; HUMAN EXPERIMENT; INFLAMMATION; INJECTION SITE EXTRAVASATION; INJECTION SITE HEMATOMA; INJECTION SITE PAIN; INJECTION SITE REACTION; LEG PAIN; LEUKOCYTE COUNT; LIFESTYLE MODIFICATION; MALE; MULTIPLE CYCLE TREATMENT; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PHYSICAL EXAMINATION; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTHROMBIN TIME; SIDE EFFECT; TEA; VITAL SIGN; ADOLESCENT; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; BLOOD; CLINICAL TRIAL; DRUG EFFECTS; RANDOMIZED CONTROLLED TRIAL; YOUNG ADULT;

ACUTE-PHASE REACTION; ADOLESCENT; ADULT; C-REACTIVE PROTEIN; CHEMOKINE CCL2; E-SELECTIN; ENDOTOXINS; FIBRIN FIBRINOGEN DEGRADATION PRODUCTS; HEALTHY VOLUNTEERS; HUMANS; INTERLEUKIN-6; MALE; OLIGONUCLEOTIDES; OLIGONUCLEOTIDES, ANTISENSE; PEPTIDE FRAGMENTS; PROTHROMBIN; TUMOR NECROSIS FACTOR-ALPHA; YOUNG ADULT;

EID: 84939461925     PISSN: None     EISSN: 20479980     Source Type: Journal    
DOI: 10.1161/JAHA.114.001084     Document Type: Article

References (33)

1. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111:1805-1812.
2. Black S, Kushner I, Samols D. C-reactive protein. J Biol Chem. 2004;279: 48487-48490.
3. Castell JV, Gómez-Lechón MJ, David M, Fabra R, Trullenque R, Heinrich PC. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology. 1990;12:1179-1186.
4. Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sohail M, Krausz T, Pepys MB. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med. 1999;190:1733-1740.
5. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973-979.
6. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-843.
7. Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010; 375:132-140.
8. Bisoendial RJ, Kastelein JJ, Levels JH, Zwaginga JJ, van den Bogaard B, Reitsma PH, Meijers JC, Hartman D, Levi M, Stroes ES. Activation of inflammation and coagulation after infusion of C-reactive protein in humans. Circ Res. 2005;96:714-716.
9. Bisoendial RJ, Kastelein JJ, Peters SL, Levels JH, Birjmohun R, Rotmans JI, Hartman D, Meijers JC, Levi M, Stroes ES. Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects. J Lipid Res. 2007;48:952-960.
10. Birjmohun RS, Bisoendial RJ, van Leuven SI, Ackermans M, Zwinderman A, Kastelein JJ, Stroes ES, Sauerwein HP. A single bolus infusion of C-reactive protein increases gluconeogenesis and plasma glucose concentration in humans. Metabolism. 2007;56:1576-1582.
11. Lane T, Wassef NL, Poole S, Mistry Y, Lachmann H, Gillmore J, Hawkins PN, Pepys MB. Infusion of pharmaceutical grade natural human C reactive protein is not pro inflammatory in healthy adult human volunteers. Circ Res. 2014; 114:672-676.
12. Crooke ST, Vickers T, Lima WH. Mechanisms of antisense drug action, an introduction. In: Crooke ST, ed. Antisense Drug Technology: Principles, Strategies, and Applications. 2nd ed. Boca Raton, FL: CRC Press/Taylor & Francis Group; 2007:3-46.
13. Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol. 2010;50:259-293.
14. Yu RZ, Grundy JS, Geary RS. Clinical pharmacokinetics of second generation antisense oligonucleotides. Expert Opin Drug Metab Toxicol. 2013;9:169-182.
15. Bennett CF. Pharmacological properties of 20-O-methoxyethyl-modified oligonucleotides. In: Crooke ST, ed. Antisense Drug Technology: Principles, Strategies, and Applications. 2nd ed. Boca Raton, FL: CRC Press/Taylor & Francis Group; 2007:273-303.
16. Wu H, Lima WF, Zhang H, Fan A, Sun H, Crooke ST. Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs. J Biol Chem. 2004;279:17181-17189.
17. Crooke R, Baker B, Wedel M. Cardiovascular therapeutic applications. In: Crooke ST, ed. Antisense Drug Technology: Principles, Strategies, and Applications. 2nd ed. Boca Raton, FL: CRC Press/Taylor & Francis Group; 2007:626-628.
18. Jones NR, Pegues MA, McCrory MA, Singleton W, Bethune C, Baker BF, Norris DA, Crooke RM, Graham MJ, Szalai AJ. A selective inhibitor of human Creactive protein translation is efficacious in vitro and in C-reactive protein transgenic mice and humans. Mol Ther Nucleic Acids. 2012;1:e52 doi: 10.1038/mtna.2012.44.
19. Suffredini AF, Hochstein HD, McMahon FG. Dose-related inflammatory effects of intravenous endotoxin in humans: evaluation of a new clinical lot of Escherichia coli O:113 endotoxin. J Infect Dis. 1999;179:1278-1282.
20. van Deventer SJH, Büller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood. 1990;76:2520-2526.
21. Andreasen AS, Krabbe KS, Krogh-Madsen R, Taudorf S, Pedersen BK, Møller K. Human endotoxemia as a model of systemic inflammation. Curr Med Chem. 2008;15:1697-1705.
22. Hudgins LC, Parker TS, Levine DM, Gordon BR, Saal SD, Jiang XC, Seidman CE, Tremaroli JD, Lai J, Rubin AL. A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers. J Lipid Res. 2003;44:1489-1498.
23. C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC), Wensley F, Gao P, Burgess S, Kaptoge S, Di Angelantonio E, Shah T, Engert JC, Clarke R, Davey-Smith G, Nordestgaard BG, Saleheen D, Samani NJ, Sandhu M, Anand S, Pepys MB, Smeeth L, Whittaker J, Casas JP, Thompson SG, Hingorani AD, Danesh J. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ. 2011;342:d548.
24. Ridker PM. Targeting inflammatory pathways for the treatment of cardiovascular disease. Eur Heart J. 2014;35:540-543.
25. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1b inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597-605.
26. Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, Zaharris E, Gupta M, Clearfield M, Libby P, Hasan AA, Glynn RJ, Ridker PM. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013;166:199-207.
27. Ridker PM. Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT). J Thromb Haemost. 2009;7(suppl 1):332-339.
28. IL6R Genetics Consortium Emerging Risk Factors Collaboration, Sarwar N, Butterworth AS, Freitag DF, Gregson J, Willeit P, Gorman DN, Gao P, Saleheen D, Rendon A, Nelson CP, Braund PS, Hall AS, Chasman DI, Tybjærg-Hansen A, Chambers JC, Benjamin EJ, Franks PW, Clarke R, Wilde AA, Trip MD, Steri M, Witteman JC, Qi L, van der Schoot CE, de Faire U, Erdmann J, Stringham HM, Koenig W, Rader DJ, Melzer D, Reich D, Psaty BM, Kleber ME, Panagiotakos DB, Willeit J, Wennberg P, Woodward M, Adamovic S, Rimm EB, Meade TW, Gillum RF, Shaffer JA, Hofman A, Onat A, Sundström J, Wassertheil-Smoller S, Mellström D, Gallacher J, Cushman M, Tracy RP, Kauhanen J, Karlsson M, Salonen JT, Wilhelmsen L, Amouyel P, Cantin B, Best LG, Ben-Shlomo Y, Manson JE, Davey-Smith G, de Bakker PI, O'Donnell CJ, Wilson JF, Wilson AG, Assimes TL, Jansson JO, Ohlsson C, Tivesten Á, Ljunggren Ö, Reilly MP, Hamsten A, Ingelsson E, Cambien F, Hung J, Thomas GN, Boehnke M, Schunkert H, Asselbergs FW, Kastelein JJ, Gudnason V, Salomaa V, Harris TB, Kooner JS, Allin KH, Nordestgaard BG, Hopewell JC, Goodall AH, Ridker PM, Hólm H, Watkins H, Ouwehand WH, Samani NJ, Kaptoge S, Di Angelantonio E, Harari O, Danesh J. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet. 2012;379:1205-1213.
29. Hingorani AD, Casas JP. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012;379:1214-1224.
30. Pepys Nature 2006 Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature. 2006;440:1217-1221.
31. 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, Horton J, Mant T, Chiesa J, Ritter J, Munisamy M, 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.
32. Abrams MT, Koser ML, Seitzer J, Williams SC, DiPietro MA, Wang W, Shaw AW, Mao X, Jadhav V, Davide JP, Burke PA, Sachs AB, Stirdivant SM, Sepp-Lorenzino L. Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle: effect of dexamethasone co-treatment. Mol Ther. 2010;18:171-180.
33. Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, Munisamy M, Falzone R, Harrop J, Cehelsky J, Bettencourt BR, Geissler M, Butler JS, Sehgal A, Meyers RE, Chen Q, Borland T, Hutabarat RM, Clausen VA, Alvarez R, Fitzgerald K, Gamba-Vitalo C, Nochur SV, Vaishnaw AK, Sah DW, Gollob JA, Suhr OB. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013;369:819-829.