The Current and Future Landscape of SERCA Gene Therapy for Heart Failure: A Clinical Perspective

Human Gene Therapy

Volumn 26, Issue 5, 2015, Pages 293-304

  Hayward, Carl ^a   Banner, Nicholas R ^b   Morley Smith, Andrew ^a   Lyon, Alexander R ^a   Harding, Sian E ^c  

^a ROYAL BROMPTON HOSPITAL   (United Kingdom)

^b HAREFIELD HOSPITAL   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; CALCIUM ION; GLYCERYL TRINITRATE; IVABRADINE; NEUTRALIZING ANTIBODY; PARVOVIRUS VECTOR; PLACEBO; RETROVIRUS VECTOR; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE 2A; STROMAL CELL DERIVED FACTOR 1; UNCLASSIFIED DRUG;

CLINICAL TRIAL (TOPIC); CONGESTIVE CARDIOMYOPATHY; DRUG EFFICACY; DRUG SAFETY; ENZYME ACTIVITY; EVIDENCE BASED MEDICINE; EXCITATION CONTRACTION COUPLING; GENE EXPRESSION; GENE TARGETING; GENE THERAPY; GENE VECTOR; HEART DISEASE; HEART FAILURE; HEART FUNCTION; HOSPITALIZATION; HUMAN; IN VIVO STUDY; LABORATORY TEST; LEFT VENTRICULAR ASSIST DEVICE; NONHUMAN; PATIENT SELECTION; PHASE 1 CLINICAL TRIAL (TOPIC); QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SARCOPLASMIC RETICULUM; SUMOYLATION; SYSTOLIC HEART FAILURE; VIRAL GENE DELIVERY SYSTEM; ANIMAL; GENE TRANSFER; GENETICS; METABOLISM; METHODOLOGY; TRANSLATIONAL RESEARCH;

ANIMALS; CLINICAL TRIALS AS TOPIC; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; GENETIC VECTORS; HEART FAILURE; HUMANS; RESEARCH DESIGN; SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84929731633     PISSN: 10430342     EISSN: 15577422     Source Type: Journal    
DOI: 10.1089/hum.2015.018     Document Type: Review

References (100)

1. Takeshita S, Zheng LP, Brogi E, et al. Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 1994;93:662-670.
2. Harada K, Grossman W, Friedman M, et al. Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts. J Clin Invest 1994;94:623-630.
3. Donahue JK, Heldman AW, Fraser H, et al. Focal modification of electrical conduction in the heart by viral gene transfer. Nat Med 2000;6:1395-1398.
4. Igarashi T, Finet JE, Takeuchi A, et al. Connexin gene transfer preserves conduction velocity and prevents atrial fibrillation. Circulation 2012;125:216-225.
5. Sundararaman S, Miller TJ, Pastore JM, et al. Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure. Gene Ther 2011;18:867-873.
6. Greener ID, Sasano T, Wan X, et al. Connexin43 gene transfer reduces ventricular tachycardia susceptibility after myocardial infarction. J Am Coll Cardiol 2012;60:1103-1110.
7. Sasano T, McDonald AD, Kikuchi K, Donahue JK. Molecular ablation of ventricular tachycardia after myocardial infarction. Nat Med 2006;12:1256-1258.
8. 2+-ATPase in patients with advanced heart failure. Circulation 2011;124:304-313.
9. Zsebo KM, Yaroshinsky A, Rudy JJ, et al. Long term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circ Res 2014;114:101-108.
10. Penn MS, Mendelsohn FO, Schaer GL, et al. An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure. Circ Res 2013;112:816-825.
11. Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol 2011;8:30-41.
12. McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
13. Sikkel MB, Hayward C, MacLeod KT, et al. SERCA2a gene therapy in heart failure: an anti-arrhythmic positive inotrope. Br J Pharmacol 2014;171:38-54.
14. Barrans JD, Allen PD, Stamatiou D, et al. Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray. Am J Pathol 2002;160:2035-2043.
15. Hwang JJ, Allen PD, Tseng GC, et al. Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol Genomics 2002;10:31-44.
16. Steenbergen C, Afshari CA, Petranka JG, et al. Alterations in apoptotic signaling in human idiopathic cardiomyopathic hearts in failure. Am J Physiol Heart Circ Physiol 2003;284:H268-H276.
17. Thum T, Galuppo P, Wolf C, et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 2007;116:258-267.
18. van Rooij E, Sutherland LB, Qi X, et al. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007;316:575-579.
19. Bristow MR, Ginsburg R, Minobe W, et al. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med 1982;307:205-211.
20. Brodde OE, Schuler S, Kretsch R, et al. Regional distribution of beta-adrenoceptors in the human heart: coexistence of functional beta 1- and beta 2-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy. J Cardiovasc Pharmacol 1986;8:1235-1242.
21. Gwathmey JK, Copelas L, MacKinnon R, et al. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 1987;61:70-76.
22. Tweedie D, Harding SE, MacLeod KT. Sarcoplasmic reticulum Ca content, sarcolemmal Ca influx and the genesis of arrhythmias in isolated guinea-pig cardiomyocytes. J Mol Cell Cardiol 2000;32:261-272.
23. 2+ exchanger in end-stage human heart failure. Circ Res 1994;75:443-453.
24. 2+ leak in intact ventricular myocytes from rabbits in heart failure. Circ Res 2003;93:592-594.
25. Vermeulen JT, McGuire MA, Opthof T, et al. Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. Cardiovasc Res 1994;28:1547-1554.
26. Davia K, Davies CH, Harding SE. Effects of inhibition of sarcoplasmic reticulum calcium uptake on contraction in myocytes isolated from failing human ventricle. Cardiovasc Res 1997;33:88-97.
27. Zarain-Herzberg A, Afzal N, Elimban V, Dhalla NS. Decreased expression of cardiac sarcoplasmic reticulum Ca(2+)-pump ATPase in congestive heart failure due to myocardial infarction. Mol Cell Biochem 1996;163-164:285-290.
28. Qi M, Shannon TR, Euler DE, et al. Downregulation of sarcoplasmic reticulum Ca(2+)-ATPase during progression of left ventricular hypertrophy. Am J Physiol 1997;272:H2416-H2424.
29. Cadre BM, Qi M, Eble DM, et al. Cyclic stretch down-regulates calcium transporter gene expression in neonatal rat ventricular myocytes. J Mol Cell Cardiol 1998;30:2247-2259.
30. Hasenfuss G, Reinecke H, Studer R, et al. Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res 1994;75:434-442.
31. 2+ uptake and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation 1995;92:3220-3228.
32. 2+ ATPase and phospholamban mRNA and protein levels in end-stage heart failure due to ischemic or dilated cardiomyopathy. J Mol Med (Berl) 1996;74:321-332.
33. Andersson KB, Birkeland JA, Finsen AV, et al. Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 gene. J Mol Cell Cardiol 2009;47:180-187.
34. Davia K, Hajjar RJ, Terracciano CM, et al. Functional alterations in adult rat myocytes after overexpression of phospholamban with use of adenovirus. Physiol Genomics 1999;1:41-50.
35. Kadambi VJ, Kranias EG. Phospholamban: a protein coming of age. Biochem Biophys Res Commun 1997;239:1-5.
36. Kho C, Lee A, Jeong D, et al. SUMO1-dependent modulation of SERCA2a in heart failure. Nature 2011;477:601-605.
37. Davia K, Bernobich E, Ranu HK, et al. SERCA2A overexpression decreases the incidence of aftercontractions in adult rabbit ventricular myocytes. J Mol Cell Cardiol 2001;33:1005-1015.
38. Cutler MJ, Wan X, Laurita KR, et al. Targeted SERCA2a gene expression identifies molecular mechanism and therapeutic target for arrhythmogenic cardiac alternans. Circ Arrhythmia Electrophysiol 2009;2:686-694.
39. del Monte F, Lebeche D, Guerrero JL, et al. Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling. Proc Natl Acad Sci USA 2004;101:5622-5627.
40. 2+ATPase pump overexpression in a porcine model of ischemia reperfusion. Circulation 2008;118:614-624.
41. Lyon AR, Bannister ML, Collins T, et al. SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure. Circ Arrhythmia Electrophysiol 2011;4:362-372.
42. 2+ ATPase 2a gene delivery to restore electrical stability in the failing heart. Circulation 2012;126:2095-2104.
43. Soeller C, Cannell MB. Examination of the transverse tubular system in living cardiac rat myocytes by 2-photon microscopy and digital image-processing techniques. Circ Res 1999;84:266-275.
44. Sachse FB, Savio-Galimberti E, Goldhaber JI, Bridge JH. Towards computational modeling of excitation-contraction coupling in cardiac myocytes: reconstruction of structures and proteins from confocal imaging. Pac Symp Biocomput 2009:328-339.
45. Amsellem J, Delorme R, Souchier C, Ojeda C. Transverse-axial tubular system in guinea pig ventricular cardiomyocyte: 3D reconstruction, quantification and its possible role in K+ accumulation-depletion phenomenon in single cells. Biol Cell 1995;85:43-54.
46. Soeller C, Crossman D, Gilbert R, Cannell MB. Analysis of ryanodine receptor clusters in rat and human cardiac myocytes. Proc Natl Acad Sci USA 2007;104:14958-14963.
47. Jayasinghe ID, Cannell MB, Soeller C. Organization of ryanodine receptors, transverse tubules, and sodium-calcium exchanger in rat myocytes. Biophys J 2009;97:2664-2673.
48. Hoshijima M, Ikeda Y, Iwanaga Y, et al. Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med 2002;8:864-871.
49. Iwanaga Y, Hoshijima M, Gu Y, et al. Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Invest 2004;113:727-736.
50. Kaye DM, Preovolos A, Marshall T, et al. Percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals. J Am Coll Cardiol 2007;50:253-260.
51. del Monte F, Harding SE, Dec GW, et al. Targeting phospholamban by gene transfer in human heart failure. Circulation 2002;105:904-907.
52. Suckau L, Fechner H, Chemaly E, et al. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation 2009;119:1241-1252.
53. Haghighi K, Kolokathis F, Pater L, et al. Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J Clin Invest 2003;111:869-876.
54. Nicolaou P, Rodriguez P, Ren X, et al. Inducible expression of active protein phosphatase-1 inhibitor-1 enhances basal cardiac function and protects against ischemia/reperfusion injury. Circ Res 2009;104:1012-1020.
55. Pathak A, Baldwin B, Kranias EG. Key protein alterations associated with hyperdynamic cardiac function: insights based on proteomic analysis of the protein phosphatase 1 inhibitor-1 overexpressing hearts. Hellenic J Cardiol 2007; 48:30-36.
56. Pathak A, del Monte F, Zhao W, et al. Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1. Circ Res 2005;96:756-766.
57. Hajjar RJ, Zsebo K, Deckelbaum L, et al. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Cardiac Fail 2008;14:355-367.
58. Jaski BE, Jessup ML, Mancini DM, et al. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a first-in-human phase 1/2 clinical trial. J Card Fail 2009;15:171-181.
59. U.S. Department of Health and Human Services FDA. Center for Biologics Evaluation and Research, Center for Devices and Radiological Health Guidance for Industry. Cellular Therapy for Cardiac Disease 2010. www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/ucm164265.htm (accessed May 2015).
60. 2+-ATPase in patients with advanced heart failure. Circulation 2011;124:304-313.
61. Rogers JK, Pocock SJ, McMurray JJ, et al. Analysing recurrent hospitalizations in heart failure: a review of statistical methodology, with application to CHARM-Preserved. Eur J Heart Fail 2014;16:33-40.
62. Monahan PE, Samulski RJ. AAV vectors: is clinical success on the horizon? Gene Ther 2000;7:24-30.
63. Carter PJ, Samulski RJ. Adeno-associated viral vectors as gene delivery vehicles. Int J Mol Med 2000;6:17-27.
64. Penaud-Budloo M, Le Guiner C, Nowrouzi A, et al. Adeno-associated virus vector genomes persist as episomal chromatin in primate muscle. J Virol 2008;82:7875-7885.
65. Niemeyer GP, Herzog RW, Mount J, et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood 2009;113:797-806.
66. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000;288:669-672.
67. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003;302:415-419.
68. Klages N, Zufferey R, Trono D. A stable system for the high-titer production of multiply attenuated lentiviral vectors. Mol Ther 2000;2:170-176.
69. Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 2013;341:1233158.
70. Aiuti A, Biasco L, Scaramuzza S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 2013;341:1233151.
71. Manno CS, Arruda VR, Pierce GF, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 2006;12:342-347.
72. Hayward C, Patel H, Lyon A. Gene therapy in heart failure: SERCA2a as a therapeutic target. Circ J 2014;78:2577-2587.
73. Karakikes I, Hadri L, Rapti K, et al. Concomitant intravenous nitroglycerin with intracoronary delivery of AAV1.SERCA2a enhances gene transfer in porcine hearts. Mol Ther 2012;20:565-571.
74. Louis Jeune V, Joergensen JA, Hajjar RJ, Weber T. Preexisting anti-adeno-associated virus antibodies as a challenge in AAV gene therapy. Hum Gene Ther Methods 2013;24:59-67.
75. Klasse PJ, Sattentau QJ. Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J Gen Virol 2002;83:2091-2108.
76. Calcedo R, Vandenberghe LH, Gao G, et al. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis 2009;199:381-390.
77. Boutin S, Monteilhet V, Veron P, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther 2010;21:704-712.
78. Mingozzi F, Chen Y, Edmonson SC, et al. Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue. Gene Ther 2013;20:417-424.
79. Liu Q, Huang W, Zhao C, et al. The prevalence of neutralizing antibodies against AAV serotype 1 in healthy subjects in China: implications for gene therapy and vaccines using AAV1 vector. J Med Virol 2013;85:1550-1556.
80. Parks WP, Boucher DW, Melnick JL, et al. Seroepidemiological and ecological studies of the adenovirus-associated satellite viruses. Infect Immun 1970;2:716-722.
81. Mimuro J, Mizukami H, Shima M, et al. The prevalence of neutralizing antibodies against adeno-associated virus capsids is reduced in young Japanese individuals. J Med Virol 2014;86:1990-1997.
82. van der Marel S, Comijn EM, Verspaget HW, et al. Neutralizing antibodies against adeno-associated viruses in inflammatory bowel disease patients: implications for gene therapy. Inflamm Bowel Dis 2011;17:2436-2442.
83. Tilemann L, Ishikawa K, Weber T, Hajjar RJ. Gene therapy for heart failure. Circ Res 2012;110:777-793.
84. Lochrie MA, Tatsuno GP, Christie B, et al. Mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization. J Virol 2006;80:821-834.
85. Maheshri N, Koerber JT, Kaspar BK, Schaffer DV. Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat Biotechnol 2006;24:198-204.
86. Maersch S, Huber A, Buning H, et al. Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes. Virology 2010;397:167-175.
87. Moss RB, Rodman D, Spencer LT, et al. Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 2004;125:509-521.
88. Ma X, Cheng Z, Kong H, et al. Changes in biophysical and biochemical properties of single bronchial smooth muscle cells from asthmatic subjects. Am J Physiol Lung Cell Mol Physiol 2002;283:L1181-L1189.
89. Matsumoto H, Moir LM, Oliver BG, et al. Comparison of gel contraction mediated by airway smooth muscle cells from patients with and without asthma. Thorax 2007;62:848-854.
90. Leguillette R, Laviolette M, Bergeron C, et al. Myosin, transgelin, and myosin light chain kinase: expression and function in asthma. Am J Respir Crit Care Med 2009;179:194-204.
91. Triggle DJ. Calcium, the control of smooth muscle function and bronchial hyperreactivity. Allergy 1983;38:1-9.
92. Parameswaran K, Janssen LJ, O'Byrne PM. Airway hyperresponsiveness and calcium handling by smooth muscle: a "deeper look." Chest 2002;121:621-624.
93. Perez-Zoghbi JF, Karner C, Ito S, et al. Ion channel regulation of intracellular calcium and airway smooth muscle function. Pulm Pharmacol Ther 2009;22:388-397.
94. 2+ ATPase (SERCA) expression contributes to airway remodelling in bronchial asthma. Proc Natl Acad Sci USA 2009;106:10775-10780.
95. Hadri L, Kratlian RG, Benard L, et al. Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension. Circulation 2013;128:512-523.
96. 2+ store segregation. Cardiovasc Res 2014;103:313-323.
97. 2+ response amplitude and duration. Nature 1997;386:855-858.
98. 2+ signal, transcription factor NFAT and proliferation in human vascular smooth muscle cells. J Mol Cell Cardiol 2011;50:621-633.
99. 2+ -ATPase gene transfer reduces vascular smooth muscle cell proliferation and neointima formation in the rat. Circ Res 2005;97:488-495.
100. Merlet E, Lipskaia L, Marchand A, et al. A calcium-sensitive promoter construct for gene therapy. Gene Ther 2013;20:248-254.