Cardiac myosin activation with gene therapy produces sustained inotropic effects and may treat heart failure with reduced ejection fraction

Handbook of Experimental Pharmacology

Volumn 243, Issue , 2017, Pages 447-464

  Teichman, Sam L ^a   Thomson, Kassandra S ^b   Regnier, Michael ^b,c  

^a BEAT Biotherapeutics Corp   (United States)

^b University of Washington   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Cardiac myosin activation; dATP; Gene therapy; Heart failure; Inotropic therapy; Ribonucleotide reductase; Translational medicine

Indexed keywords

ADENO ASSOCIATED VIRUS VECTOR; BACULOVIRUS VECTOR; CALCIUM; CARDIAC MYOSIN; CREATINE KINASE; CYCLIC AMP; CYCLIC AMP PHOSPHODIESTERASE; DEOXYADENOSINE TRIPHOSPHATE; DOBUTAMINE; OMECAMTIV MECARBIL; PLASMA MEMBRANE CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; POST-TRANSLATIONALLY MODIFIED PROTEIN; RIBONUCLEOTIDE REDUCTASE; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; STROMAL CELL DERIVED FACTOR 1; 2'-DEOXYADENOSINE TRIPHOSPHATE; DEOXYADENOSINE PHOSPHATE;

CARDIAC MUSCLE CELL; CARDIOVASCULAR GENE THERAPY; CLINICAL TRIAL (TOPIC); CONGESTIVE CARDIOMYOPATHY; CONTROLLED CLINICAL TRIAL (TOPIC); DOSE RESPONSE; DRUG ACTIVATION; DRUG DELIVERY SYSTEM; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERANCE; FUNCTIONAL STATUS; GENE OVEREXPRESSION; HEART FAILURE WITH REDUCED EJECTION FRACTION; HEART MUSCLE CONTRACTILITY; HUMAN; INOTROPISM; INTERNAL MEDICINE; NONHUMAN; PARENTERAL DRUG ADMINISTRATION; PRIORITY JOURNAL; PROTEIN SYNTHESIS; QUALITY OF LIFE; SUSTAINED DRUG RELEASE; TRANSLATIONAL RESEARCH; UPREGULATION; ANIMAL; CARDIAC MUSCLE; GENE THERAPY; GENETICS; HEART CONTRACTION; HEART FAILURE; HEART STROKE VOLUME; METABOLISM; PATHOPHYSIOLOGY; PROCEDURES;

ANIMALS; CARDIAC MYOSINS; DEOXYADENINE NUCLEOTIDES; GENETIC THERAPY; HEART FAILURE; HUMANS; MYOCARDIAL CONTRACTION; MYOCARDIUM; STROKE VOLUME;

EID: 85020637931     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/164_2016_31     Document Type: Chapter

References (39)

1. Ahmad MF, Dealwis CG (2013) The structural basis for the allosteric regulation of ribonucleotide reductase. Prog Mol Biol Transl Sci 117:389–410
2. Ambardekar AV, Buttrick PM (2011) Reverse remodeling with left ventricular assist devices: a review of clinical, cellular, and molecular effects. Circ Heart Fail 4(2):224–233
3. Arnett AL, Beutler LR, Quintana A et al (2013) Heparin-binding correlates with increased efficiency of AAV1- and AAV6-mediated transduction of striated muscle, but negatively impacts CNS transduction. Gene Ther 20(5):497–503
4. Baker AJ (2011) Refueling the heart: using 2-deoxy-ATP to enhance cardiac contractility. J Mol Cell Cardiol 51(6):883–884
5. Caras IW, Martin DW (1988) Molecular cloning of the cDNA for a mutant mouse ribonucleotide reductase M1 that produces a dominant mutator phenotype in mammalian cells. Mol Cell Biol 8(7):2698–2704
6. Cheng Y, Hogarth KA, O’Sullivan ML, Regnier M, Pyle WG (2016) 2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 310(1):H80–H91
7. Cleland JG, Teerlink JR, Senior R et al (2011) The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebocontrolled, crossover, dose-ranging phase 2 trial. Lancet 378(9792):676–683
8. Cohn JN, Goldstein SO, Greenberg BH et al (1998) A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med 339(25):1810–1816
9. Dixon JA, Spinale FG (2009) Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circ Heart Fail 2(3):262–271
10. Feest ER, Steven Korte F, Tu AY et al (2014) Thin filament incorporation of an engineered cardiac troponin C variant (L48Q) enhances contractility in intact cardiomyocytes from healthy and infarcted hearts. J Mol Cell Cardiol 72:219–227
11. Francis GS, Bartos JA, Adatya S (2014) Inotropes. J Am Coll Cardiol 63(20):2069–2078
12. Gao G, Bish LT, Sleeper MM et al (2011) Transendocardial delivery of AAV6 results in highly efficient and global cardiac gene transfer in rhesus macaques. Hum Gene Ther 22(8):979–984
13. Greenberg BH, Chou W, Saikali KG et al (2015) Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina. JACC Heart Fail 3 (1):22–29
14. Ishikawa K, Tilemann L, Ladage D et al (2012) Cardiac gene therapy in large animals: bridge from bench to bedside. Gene Ther 19(6):670–677
15. Kadota S, Carey J, Reinecke H et al (2015) Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure. Eur J Heart Fail 17(8):772–781
16. Kolwicz SC, Odom GL, Nowakowski SG et al (2016) AAV6-mediated cardiac-specific overexpression of ribonucleotide reductase enhances myocardial contractility. Mol Ther 24:240–250
17. Korte FS, Dai J, Buckley K et al (2011) Upregulation of cardiomyocyte ribonucleotide reductase increases intracellular 2 deoxy-ATP, contractility, and relaxation. J Mol Cell Cardiol 51 (6):894–901
18. Lowes BD, Higginbotham M, Petrovich L et al (2000) Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group. J Am Coll Cardiol 36(2):501–508
19. Lundy SD, Murphy SA, Dupras SK et al (2014) Cell-based delivery of dATP via gap junctions enhances cardiac contractility. J Mol Cell Cardiol 72:350–359
20. Lüscher TF (2014) Heart failure: the epidemic of the new century. Eur Heart J 35(48):3389–3390
21. Malik FI, Hartman JJ, Elias KA et al (2011) Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science 331(6023):1439–1443
22. Moussavi-Harami F, Razumova MV, Racca AW, Cheng Y, Stempien-Otero A, Regnier M (2015) 2-Deoxy adenosine triphosphate improves contraction in human end-stage heart failure. J Mol Cell Cardiol 79:256–263
23. Nowakowski S, Adamek N, Geeves M et al (2013) 2-Deoxy-ATP alters myosin structure to enhance cross-bridge cycling and improve cardiac function [Abstract]. Presented at Biophysical Society 57th Annual Meeting, 2–6 February 2013, Philadelphia, PA2013
24. Nowakowski SG, Kolwicz SC, Korte FS et al (2013b) Transgenic overexpression of ribonucleotide reductase improves cardiac performance. Proc Natl Acad Sci U S A 110(15):6187–6192
25. Palomeque J, Chemaly ER, Colosi P et al (2007) Efficiency of eight different AAV serotypes in transducing rat myocardium in vivo. Gene Ther 14(13):989–997
26. Pleger ST, Brinks H, Ritterhoff J et al (2013) Heart failure gene therapy: the path to clinical practice. Circ Res 113(6):792–809
27. Redfield MM (2002) Heart failure—an epidemic of uncertain proportions. N Engl J Med 347 (18):1442–1444
28. Regnier M, Homsher E (1998) The effect of ATP analogs on posthydrolytic and force development steps in skinned skeletal muscle fibers. Biophys J 74(6):3059–3071
29. Regnier M, Lee DM, Homsher E (1998a) ATP analogs and muscle contraction: mechanics and kinetics of nucleoside triphosphate binding and hydrolysis. Biophys J 74(6):3044–3058
30. Regnier M, Martyn DA, Chase PB (1998b) Calcium regulation of tension redevelopment kinetics with 2-deoxy-ATP or low [ATP] in rabbit skeletal muscle. Biophys J 74(4):2005–2015
31. Regnier M, Rivera AJ, Chen Y, Chase PB (2000) 2-deoxy-ATP enhances contractility of rat cardiac muscle. Circ Res 86(12):1211–1217
32. Regnier M, Martin H, Barsotti RJ, Rivera AJ, Martyn DA, Clemmens E (2004) Cross-bridge versus thin filament contributions to the level and rate of force development in cardiac muscle. Biophys J 87(3):1815–1824
33. Schoffstall B, Chase PB (2008) Increased intracellular [dATP] enhances cardiac contraction in embryonic chick cardiomyocytes. J Cell Biochem 104(6):2217–2227
34. Schoffstall B, Clark A, Chase PB (2006) Positive inotropic effects of low dATP/ATP ratios on mechanics and kinetics of porcine cardiac muscle. Biophys J 91(6):2216–2226
35. Solomon SD, Foster E, Bourgoun M et al (2010) Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy. Circulation 122(10):985–992
36. Teerlink JR (2009) A novel approach to improve cardiac performance: cardiac myosin activators. Heart Fail Rev 14(4):289–298
37. Teerlink JR, Felker GM, McMurry JJV et al (2016) Acute treatment with omecamtiv mecarbil to increase contractility in acute heart failure. The ATOMIC-AHF Study. J Am Coll Cardiol 67:1444–1455
38. Tilemann L, Ishikawa K, Weber T, Hajjar RJ (2012) Gene therapy for heart failure. Circ Res 110 (5):777–793
39. Yancy CW, Jessup M, Bozkurt B et al (2013) 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 62(16):e147–e239