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dc.contributor.author
Denegri, Marco
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Bongianino, Rossana
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Lodola, Francesco
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Boncompagni, Simona
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de Giusti, Verónica Celeste
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Avelino Cruz, José E.
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Liu, Nian
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Persampieri, Simone
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Curcio, Antonio
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Esposito, Francesca
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Pietrangelo, Laura
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Marty, Isabelle
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Villani, Laura
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Moyaho, Alejandro
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Baiardi, Paola
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Auricchio, Alberto
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Protasi, Feliciano
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Napolitano, Carlo
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Priori, Silvia G.
dc.date.available
2017-02-07T17:30:12Z
dc.date.issued
2014-06
dc.identifier.citation
Denegri, Marco; Bongianino, Rossana; Lodola, Francesco; Boncompagni, Simona; de Giusti, Verónica Celeste; et al.; Single delivery of an Adeno-Associated viral Construct to Transfer the CASQ2 Gene to Knock-In Mice Affected by Catecholaminergic Polymorphic Ventricular Tachycardia Is Able to Cure the Disease From Birth to Advanced Age; American Heart Association; Circulation; 129; 25; 6-2014; 2673-2681
dc.identifier.issn
0009-7322
dc.identifier.uri
http://hdl.handle.net/11336/12649
dc.description.abstract
Background — Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is therefore a need to explore the curative potential of gene therapy for this disease. We investigated the efficacy and durability of viral gene transfer of the calsequestrin 2 (CASQ2) wild-type gene in a catecholaminergic polymorphic ventricular tachycardia knock-in mouse model carrying the CASQ2R33Q/R33Q (R33Q) mutation.
Methods and Results — We engineered an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of CASQ2 wild-type (AAV9-CASQ2) plus the green fluorescent protein (GFP) gene to infect newborn R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to investigate the ability of the infection to prevent the disease and adult R33Q mice studied after 2 months to assess whether the AAV9-CASQ2 delivery could revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In both protocols, we observed the restoration of physiological expression and interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological and ultrastructural abnormalities in calcium release units present in R33Q mice; and the lack of life-threatening arrhythmias.
Conclusions — Our data demonstrate that viral gene transfer of wild-type CASQ2 into the heart of R33Q mice prevents and reverts severe manifestations of catecholaminergic polymorphic ventricular tachycardia and that this curative effect lasts for 1 year after a single injection of the vector, thus posing the rationale for the design of a clinical trial.
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application/pdf
dc.language.iso
eng
dc.publisher
American Heart Association
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Arrhythmias
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Functional Recovery
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Gene Theraphy
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Calsequestrin
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Otras Medicina Básica
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Single delivery of an Adeno-Associated viral Construct to Transfer the CASQ2 Gene to Knock-In Mice Affected by Catecholaminergic Polymorphic Ventricular Tachycardia Is Able to Cure the Disease From Birth to Advanced Age
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
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info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-01-25T13:57:48Z
dc.journal.volume
129
dc.journal.number
25
dc.journal.pagination
2673-2681
dc.journal.pais
Estados Unidos
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Dallas
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Fil: Denegri, Marco. Fondazione Salvatore Maugeri; Italia
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Fil: Bongianino, Rossana. Fondazione Salvatore Maugeri; Italia
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Fil: Lodola, Francesco. Fondazione Salvatore Maugeri; Italia
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Fil: Boncompagni, Simona. University G. d’Annunzio; Italia
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Fil: de Giusti, Verónica Celeste. Fondazione Salvatore Maugeri; Italia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
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Fil: Avelino Cruz, José E.. Fondazione Salvatore Maugeri; Italia. Benemerita Universidad Autonoma de Puebla; México
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Fil: Liu, Nian. Capital Medical University; China
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Fil: Persampieri, Simone. Fondazione Salvatore Maugeri; Italia
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Fil: Curcio, Antonio. Fondazione Salvatore Maugeri; Italia. University of Magna Graecia; Italia
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Fil: Esposito, Francesca. Fondazione Salvatore Maugeri; Italia. Università Degli Studi Di Napoli Federico Ii; Italia
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Fil: Pietrangelo, Laura. University G. d’Annunzio; Italia
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Fil: Marty, Isabelle. Grenoble Institut des Neurosciences; Francia. Universite Joseph Fourier; Francia
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Fil: Villani, Laura. Fondazione Salvatore Maugeri; Italia
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Fil: Moyaho, Alejandro. Benemerita Universidad Autonoma de Puebla; México
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Fil: Baiardi, Paola. Fondazione Salvatore Maugeri; Italia
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Fil: Auricchio, Alberto. Telethon Institute of Genetics and Medicine; Italia. Università Degli Studi Di Napoli Federico Ii; Italia
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Fil: Protasi, Feliciano. University G. d’Annunzio; Italia
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Fil: Napolitano, Carlo. Fondazione Salvatore Maugeri; Italia
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Fil: Priori, Silvia G.. Fondazione Salvatore Maugeri; Italia. University of Pavia; Italia
dc.journal.title
Circulation
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1161/CIRCULATIONAHA.113.006901
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info:eu-repo/semantics/altIdentifier/url/http://circ.ahajournals.org/content/129/25/2673
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