IMPACT-Hop on

Arrhythmogenic Cardiomyopathy (ACM) is a genetic disease with no effective treatment available, predisposing patients to ventricular arrhythmias and sudden cardiac death. ACM is characterized by progressive cardiomyocyte loss and fibrofatty replacement, often starting in the epicardium. While epicardial abnormalities may represent early ACM signs, the mechanisms driving fibrofatty tissue accumulation remain unclear. Also, a major challenge is that most ACM animal models do not naturally develop the cardiac adipose tissue seen in humans and many in vitro heart models lack the epicardium layer in its complexity. With IMPACT-Hop On, AccelBio will bring a unique and complementary humanized heart organoid model (Epi-HO) to the IMPACT EIC Pathfinder consortium, which replicates the epicardium-myocardium structure observed in the adult human heart. Generation of Epi-HO carrying ACM mutations (ACM-Epi-HO) will create a new Work Package (WP10) focused on the epicardial–to–fibro-fatty transition. ACM-Epi-HOs will be generated and characterized to uncover new mechanisms of action, biomarkers and therapeutic targets. New molecular and structural data will be incorporated into previous IMPACT tasks, feeding the AI-assisted comparative analysis of ACM models and contribute to patient stratification. ACM-Epi-HOs will also aid in identifying and validating therapeutic compounds to prevent epicardial abnormalities. AccelBio’s expertise on translational research and the uniqueness of its Epi-HO model will strongly potentiate IMPACT’s outcomes and accelerate the development of first in class ACM therapies. Additionally, through organization of research, business and society-oriented activities, AccelBio will potentiate IMPACT’s dissemination and exploitation plan. Conversely, with IMPACT-Hop On, AccelBio will gain new competencies in project management and coordination, increase its participation in transnational projects and reinforce its network within EU biotechnology R&I ecosystem