Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of cardiac failure. Cytoprotective gene therapy with the Vascular Endothelial Growth Factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs [1,2]. The aim of this work was to test the tolerability and feasibility of intracoronary inoculation under fluoroscopic guidance of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessment at 7 days post-procedure in all dogs showed stable clinical conditions that could be superimposed to those pre-procedure. The results of this work indicate that intracoronary gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this procedure on disease progression. [1] Woitek et al. Intracoronary Cytoprotective Gene Therapy, Journal of the American College of Cardiology; 66(2):139-153, 2015 [2] Pepe et al. Intramyocardial VEGF-B167 gene delivery delays the progression towards congestive failure in dogs with pacing-induced dilated cardiomyopathy. Circulation Research;106(12):1893-1903, 2010

INTRACORONARY CYTOPROTECTIVE GENE THERAPY IN CANINE PATIENTS WITH DILATED CARDIOMYOPATHY

Carlucci Lucia;Staffieri Francesco;Lacitignola Luca;Ceci Luigi;Iarussi Fabrizio;Crovace Antonio;
2018

Abstract

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of cardiac failure. Cytoprotective gene therapy with the Vascular Endothelial Growth Factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs [1,2]. The aim of this work was to test the tolerability and feasibility of intracoronary inoculation under fluoroscopic guidance of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessment at 7 days post-procedure in all dogs showed stable clinical conditions that could be superimposed to those pre-procedure. The results of this work indicate that intracoronary gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this procedure on disease progression. [1] Woitek et al. Intracoronary Cytoprotective Gene Therapy, Journal of the American College of Cardiology; 66(2):139-153, 2015 [2] Pepe et al. Intramyocardial VEGF-B167 gene delivery delays the progression towards congestive failure in dogs with pacing-induced dilated cardiomyopathy. Circulation Research;106(12):1893-1903, 2010
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/247686
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