Cardiovascular diseases (CVD) represent a major cause of morbidity and mortality. The best current therapy reduces CV risk by only 25-30% and remains ineffective in reducing the excess risk associated with several co-morbidities. Therefore, there is considerable need for new therapies to limit the burden of CVD. Based on a current ERC Starting Grant project, the applicant’s group proposed and validated the concept that mature B lymphocytes are instrumental in the orchestration of the inflammatory response after ischemic myocardial injury, in part through production of CCL7 chemokine and mobilisation/recruitment of inflammatory monocytes to the infarction site (Zouggari Y et al., Nat Med 2013). Our goal now is to translate this ground-breaking discovery and novel therapeutic concept into benefit for patients. The overall objective of the RITA-MI project is to develop a new and cost-effective therapy for patients with acute myocardial infarction (MI) based on selective targeting of the B cell immune response, with the ultimate aim to substantially reduce the high risk of death and major cardiovascular events associated with the disease. Interestingly, the drug, CD20 monoclonal antibody (mAb) rituximab, is readily available for testing in a re-purposing scheme, allowing for rapid initiation of this proof-of-concept clinical trial. Working Hypothesis: A single infusion of rituximab at the acute phase of MI is safe, substantially depletes circulating B cells, and has the potential to limit infarction size and improves myocardial heart function. Overall objective: Does a ‘fire and forget’ approach with rituximab (a single intravenous infusion) reduce infarct size and/or improve heart function in patients with acute STEMI? The overall aim will be pursued through a series of specific objectives, which will correspond to a first step of a dose-finding proof-of-concept study (the present RITA-MI project), followed (if successful) by a phase II clinical efficacy trial.

RITA-MI 2 will assess the impact of a novel therapeutic strategy targeting patients’ immune response on the recovery of heart function after myocardial infarction (MI) in a phase 2 clinical trial. Cardiovascular diseases (CVD) represent a major cause of morbidity and mortality worldwide. Despite important advances in the treatment of acute MI, the occurrence of MI still results in left ventricular dysfunction in up to 50% of patients, which leads to the development of heart failure. Left ventricular dysfunction is the strongest predictor of adverse outcome after acute MI, and is associated with a 3 to 4-fold increase in mortality risk. In Westernised countries, heart failure is responsible for 1-2% of all health expenditure, which is mostly driven by repeated hospital admissions. Therefore, there is a considerable need for new therapies to limit the burden of CVD. This application builds on a ground-breaking discovery by a unique team of clinicians and scientists who provided extensive validation for their findings through a series of basic, pre-clinical and translational research. Our goal is to translate this discovery into benefit for patients. The new therapy is based on selective targeting of a specific immune cell subset, mature B lymphocytes, with the aim to limit deleterious cardiac remodelling and improve heart function recovery post-MI. Of note, the drug that targets this pathway, i.e., CD20 monoclonal antibody (mAb) rituximab, is available for testing in a re-purposing scheme, allowing for rapid initiation of proof-of-concept clinical trials. The PIs of the present proposal have successfully completed a phase 1/2a clinical trial (RITA-MI, NCT03072199), which established the safety of rituximab treatment at the acute phase of MI. RITA-MI 2 will conduct a phase 2b randomised double-blind placebo-controlled CT to assess the impact of B cell depletion with the CD20 mAb rituximab on left ventricular dysfunction and cardiac remodelling after acute MI.

Track&Know will research, develop and exploit a new software framework that aims at increasing the efficiency of Big Data applications in the transport, mobility, motor insurance and health sectors. Stemming from industrial cases, Track&Know will develop user friendly toolboxes that will be readily applicable in the addressed markets, and will be also investigated in additional domains through liaison activities with running ICT-15 Lighthouse projects. Track&Know integrates multidisciplinary research teams from Mobility Data management, Complex Event Recognition, Geospatial Modelling, Complex Network Analysis, Transportation Engineering and Visual Analytics to develop new models and applications. Track&Know recognizes that Big Data penetration is not adequately developed in niche markets outside the traditional verticals (e.g. Finance) and so the Track&Know Toolboxes will be demonstrated in three real-world Pilots using datasets from niche market scenarios to validate efficiency improvements. Performance and impact benchmarks are elaborated and will be documented during pilots deployment. The Track&Know consortium is composed by complementary partners, coming from addressed research, technological and commercial domains, that have a proven track record of high quality research capacity. Thus, the carefully structured workplan, embodies a holistic approach towards meeting the Track&Know objectives and delivering market-relevant outcomes of significant exploitation potential.