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EU-rhythmy SIGNED

Molecular strategies to treat inherited arrhythmias

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

EU-rhythmy project word cloud

Explore the words cloud of the EU-rhythmy project. It provides you a very rough idea of what is the project "EU-rhythmy" about.

gene diseases western individuals pi inherited prevention knock arrhythmogenic rhythm critical pioneer artery catecholaminergic intends clinically severe model older syndrome tachycardia death therapies bases qt heart inhomogeneity clinical younger molecular broad cpvt successful proarrhythmic valuable disturbances therapy subjects protein ventricular milieu silencing disease rewarding acquired sudden arrhythmias events constructs engineer coronary countries efficacy strategies expression 25 editing effort risk pig dominant regional team promoters unexplored electrical carefully cardiac lqt8 polymorphic envisioned translation innovative heritable scd core benefit virtually

Project "EU-rhythmy" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITA DEGLI STUDI DI PAVIA Organization address address: STRADA NUOVA 65 city: PAVIA postcode: 27100 website: www.unipv.it contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Italy [IT]
Total cost	2˙314˙029 €
EC max contribution	2˙314˙029 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2014-ADG
Funding Scheme	ERC-ADG
Starting year	2015
Duration (year-month-day)	from 2015-11-01 to 2020-10-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITA DEGLI STUDI DI PAVIA UNIVERSITA DEGLI STUDI DI PAVIA Organization address address: STRADA NUOVA 65 city: PAVIA postcode: 27100 website: www.unipv.it contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	IT (PAVIA)	coordinator	1˙334˙029.00
2	CENTRO NACIONAL DE INVESTIGACIONESCARDIOVASCULARES CARLOS III (F.S.P.) CENTRO NACIONAL DE INVESTIGACIONESCARDIOVASCULARES CARLOS III (F.S.P.) Organization address address: CALLE MELCHOR FERNANDEZ ALMAGRO 3 city: MADRID postcode: 28029 website: www.cnic.es contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	ES (MADRID)	participant	600˙000.00
3	AVANTEA srl AVANTEA srl Organization address address: via Cabrini 12 city: Cremona postcode: 26100 website: www.avantea.it contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	IT (Cremona)	participant	380˙000.00

Map

Project objective

Sudden cardiac death (SCD) is a leading cause of death in western countries: coronary artery disease is the major cause of SCD in older subjects while inherited arrhythmogenic diseases are the leading cause of SCD in younger individuals. After 25 years dedicated to research of the molecular bases of heritable arrhythmias, the PI of this proposal now intends to pioneer gene therapy for prevention of SCD: a virtually unexplored field. The development of molecular therapies for rhythm disturbances is a high risk effort however, if successful, it will be highly rewarding. The PI has envisioned an ambitious and comprehensive project to target two severe inherited arrhythmogenic diseases: dominant catecholaminergic polymorphic ventricular tachycardia (CPVT) and Long QT syndrome type 8 (LQT8). The availability of a clinically relevant model is critical to ensure clinical translation of results: the team will exploit an existing CPVT model and will engineer a knock-in pig to model LQT8. The PI and her team will investigate innovative strategies of gene-delivery, gene-silencing and gene-editing to the heart comparing efficacy of different constructs and promoters. The team will also carefully engineer novel gene-therapy approaches to avoid the development of regional inhomogeneity in protein expression that may facilitate proarrhythmic events. Such a comprehensive approach will provide a most valuable core of knowledge on the comparative efficacy of a broad range of molecular strategies on the electrical milieu of the heart. It is expected that these results will not only benefit CPVT and LQT8 but rather they will foster development of gene therapy for other inherited and acquired arrhythmias.

Publications

List of publications.
year	authors and title	journal	last update
2017	Rossana Bongianino, Marco Denegri, Andrea Mazzanti, Francesco Lodola, Alessandra Vollero, Simona Boncompagni, Silvia Fasciano, Giulia Rizzo, Damiano Mangione, Serena Barbaro, Alessia Di Fonso, Carlo Napolitano, Alberto Auricchio, Feliciano Protasi, Silvia G. Priori Allele-Specific Silencing of Mutant mRNA Rescues Ultrastructural and Arrhythmic Phenotype in Mice Carriers of the R4496C Mutation in the Ryanodine Receptor Gene ( RYR2 )Novelty and Significance published pages: 525-536, ISSN: 0009-7330, DOI: 10.1161/CIRCRESAHA.117.310882	Circulation Research 121/5	2020-04-23

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