Molecular Genetics, Pathogenesis and Protein-Replacement Therapy in Arrhythmogenic Cardiomyopathy

European Coordinator:
  • WILLIAM MCKENNA, University College of London, London, United Kingdom
North American Coordinator:
  • Ali J. MARIAN, University of Texas Health Sciences Center and Texas Heart Institute, Houston, Texas, USA
Members:

Hans CLEVERS, Hubrecht Institute, Utrecht, Netherlands
David KELSELL, Queen Mary University of London, London, United Kingdom
Luisa MESTRONI, University of Colorado at Denver,  Denver, Colorado, USA
Orfeo SBAIZERO, University of Trieste, Trieste, Italy
Gianfranco SINAGRA, University of Trieste, Trieste, Italy
Matthew TAYLOR, University of Colorado at Denver,  Denver, Colorado, USA
Thomas WEBER, Icahn School of Medicine at Mount Sinai, New York, New York, USA

This network is designed to delineate the molecular genetics, genomics, and pathogenesis of arrhythmogenic cardiomyopathy (AC). The classic right-dominant form of AC, known as arrhythmogenic right ventricular cardiomyopathy, is a leading cause of sudden cardiac death in young people. The burden of AC is almost certainly underestimated, however, owing to frequent missed diagnoses and under-recognition of the left-dominant and biventricular subtypes. Initially in this disease, the heart has a normal structure and function and as the disease progresses, there is ventricular dilation, dysfunction and aneurysm formation. Clinical heart failure is a late manifestation.  A switch in the fate and differentiation of a subset of cardiac resident cells to fibro-adipocyte is the pathological hallmark of AC. The present challenge lies in elucidating the intervening steps – from mutation to pathologically overt disease – and identifying therapeutic targets therein. This network pooling resources and sharing expertise will have acess to a well phenotyped AC patient population. They will continue searching for new genes and new mutations, but most important of all, they will investigate protein replacement in transgenic mouse models to reverse the phenotype. The synergistic interactions between clinicians and scientists in this network will ultimately improve the quality of life and survival of AC patients.