The PRIORITY international network of excellence has just been awarded an $8,000,000 grant from the Fondation Leducq. PRIORITY is a research consortium of 8 partners, 4 from Europe and 4 from North America*, which will work on LMNA gene-related dilated cardiomyopathy (LMNA-DCM). PRIORITY will be coordinated by Dr Gisèle Bonne (Institut de Myologie, France) and Prof Andrew Landstrom (Duke University School of Medicine, USA). PRIORITY’s ambition over the next 5 years is 1/ to identify and characterise a large cohort of patients suffering from LMNA-DCM at international level and 2/ to propose therapeutic approaches, in order to reach the threshold of a clinical trial.
The disease
The LMNA gene encodes nuclear envelope proteins called A/C lamins, which help to maintain the structure of the cell nucleus. Through their interactions with multiple partners, lamins A/C play a key role in the organisation of chromatin, gene expression and the cytoskeleton. Mutations in the LMNA gene lead in the majority of cases to the development of dilated heart disease (LMNA-DCM), a serious hereditary disease for which there is currently no effective treatment.
The project
PRIORITY has three main objectives: (i) to study the natural history of heart disease in as many patients as possible, recruited from the OPALE**** register set up by the Institute of Myology for France, and to identify biomarkers and factors influencing the severity and progression of the disease; (ii) to explore the underlying mechanisms leading to the development of the disease; (iii) to develop therapeutic approaches aimed at correcting the mutation by gene therapy but also based on modulation of the deregulated mechanisms previously identified.
The research teams
The Fondation Leducq insists that the teams involved recruit and promote young researchers, encourage exchanges between laboratories and meet regularly each year at meetings to enhance their training and create their network.
The French teams involved in the project are researchers from the Institute of Myology: Gisèle Bonne** and Anne Bertrand**, Antoine Muchir***, Anne Forand*** and Cécile Peccate*** from the Center of Research in Myology, and Karim Wahbi and Rabah Ben Yaou**** for the OPALE register.
The PRIORITY project will start at the beginning of 2025.
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* These are research teams based in France, the USA, the Netherlands and Switzerland.
** Team 1: Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus led by Gisele Bonne
*** Team 9: Signaling pathways & striated muscles led by Antoine Muchir
**** Further details on OPALE register
***** Team Registries and databases led by Karim Wahbi
