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.
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 CASQ2(R33Q/R33Q) (R33Q) mutation.
  
  
  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.
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Marco
authors.initials: M
authors.lastname: Denegri
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Rossana
authors.initials: R
authors.lastname: Bongianino
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Francesco
authors.initials: F
authors.lastname: Lodola
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Simona
authors.initials: S
authors.lastname: Boncompagni
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Verónica C
authors.initials: VC
authors.lastname: De Giusti
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: José E
authors.initials: JE
authors.lastname: Avelino-Cruz
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Simone
authors.initials: S
authors.lastname: Persampieri
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Francesca
authors.initials: F
authors.lastname: Esposito
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Laura
authors.initials: L
authors.lastname: Pietrangelo
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marty
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Laura
authors.initials: L
authors.lastname: Villani
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Alejandro
authors.initials: A
authors.lastname: Moyaho
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Paola
authors.initials: P
authors.lastname: Baiardi
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Feliciano
authors.initials: F
authors.lastname: Protasi
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.).
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.affiliation: From Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (M.D., R.B., F.L., V.C.D.G., J.E.A.-C., S.P., A.C., F.E., P.B., C.N., S.G.P.); CeSI-Center for Research on Ageing & DNI-Department of Neuroscience and Imaging, University G. d'Annunzio, Chieti, Italy (S.B., L.P., F.P.); Facultad de Ciencias Médicas, Centro de Investigaciones Cardiovasculares, UNLP-CONICET, La Plata, Argentina (V.C.D.G.); Laboratorio de Cardiología Molecular, Insituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (J.E.A.-C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (N.L.); Division of Cardiology, Department of Medical and Surgical Science, University of "Magna Graecia," Catanzaro, Italy (A.C.); Federico II University of Naples, Cardiology, Naples, Italy (F.E.); INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France (I.M.); Université Joseph Fourier, Grenoble, France (I.M.); Pathology Division, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy (L.V.); Laboratorio de Ecología de la Conducta, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México (A.M.); Telethon Institute of Genetics and Medicine, Naples, Italy (A.A.); Medical Genetics, Department of Translational Medicine, "Federico II" University, Naples, Italy (A.A.); and Department of Molecular Medicine, University of Pavia, Pavia, Italy (S.G.P.). silvia.priori@fsm.it.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
mesh_terms: D000375:Aging; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002155:Calsequestrin / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D002135:Calcium-Binding Proteins; D002155:Calsequestrin; D002352:Carrier Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C514388:casq2 protein, mouse; C070048:triadin; C498841:Asph protein, mouse; D006899:Mixed Function Oxygenases
keywords: arrhythmias, cardiac; calsequestrin; death, sudden; genetic therapy; recovery of function