Project description DEENESFRITPL Targeting mitochondria dysfunction in cardiotoxicity following cancer treatment Cancer treatment can lead to cardiac toxicity and eventually heart failure in nearly 30 % of the cases. However, existing therapies for cancer treatment-induced cardiotoxicity (CTiCT) are suboptimal and initiated too late. The EU-funded MATRIX project is working under the hypothesis that CTiCT is associated with altered mitochondrial dynamics in cardiomyocytes and proposes to revert metabolic reprogramming as a treatment. Researchers have developed an algorithm-based imaging technique for the early detection of myocardial damage and the prompt initiation of therapy. Moreover, they plan to transplant mitochondria to address mitochondrial dysfunction in end-stage CTiCT. Show the project objective Hide the project objective Objective Cardiac toxicity is one of the most frequent serious side effects of cancer therapy, affecting up to 30% of treated patients. Cancer treatment-induced cardiotoxicity (CTiCT) can result in severe heart failure. The trade-off between cancer and chronic heart failure is an immense personal burden with physical and psychological consequences. Current therapies for CTiCT are suboptimal, featuring poor early detection algorithms and nonspecific heart failure treatments. Based on our recently published results and additional preliminary data presented here, we propose that CTiCT is associated with altered mitochondrial dynamics, triggering a cardiomyocyte metabolic reprogramming. MATRIX represents a holistic approach to tackling mitochondrial dysfunction in CTiCT. Our hypothesis is that reverting metabolic reprogramming by shifting mitochondrial substrate utilization could represent a new paradigm in the treatment of early-stage CTiCT. By refining a novel imaging-based algorithm recently developed in our group, we will achieve very early detection of myocardial damage in patients treated with commonly prescribed cancer therapies, long before clinically used parameters become abnormal. Such early detection, not available currently, is crucial for implementation of early therapies. We also hypothesize that in end-stage CTiCT, mitochondrial dysfunction has passed a no-return point, and the failing heart will only be rescued by a strategy to replenish the myocardium with fresh healthy mitochondria. This will be achieved with a radical new therapeutic option: in-vivo mitochondrial transplantation. The MATRIX project has broad translational potential, including a new therapeutic approach to a clinically relevant condition, the development of technology for early diagnosis, and advances in knowledge of basic disease mechanisms. Fields of science medical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicinecardiologymedical and health sciencesclinical medicinetransplantation Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-COG - ERC Consolidator Grant Call for proposal ERC-2018-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Net EU contribution € 1 473 437,50 Address CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid Spain See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 473 437,50 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Spain Net EU contribution € 1 473 437,50 Address CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 473 437,50 INSTITUTO INVESTIGACION SANITARIA FUNDACION JIMENEZ DIAZ Spain Net EU contribution € 525 937,50 Address AVENIDA DE LOS REYES CATOLICOS 2 28040 Madrid See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 525 937,50