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The GENIUS II (Generating Evidence-Based Pharmaceutical Targets and Drugs for Atherosclerosis) consortium is dedicated to studying atherosclerosis, the primary pathological condition underlying cardiovascular diseases. The consortium aims to translate identified druggable targets for atherosclerosis intervention into clinical applications. Gender specificity is a key consideration in all our studies. Our consortium's talent program is structured to provide young researchers with insights into the opportunities and challenges of cardiovascular drug development. The Research GENIUS II research integrates knowledge of dyslipidemia and associated immune responses. Our work is organized into distinct work packages that correspond to the logical steps in drug development. Each selected target from GENIUS I is strategically incorporated into this framework. Our investigations encompass in vitro and in vivo analyses to understand mechanisms, druggability, and effects on atherosclerosis. In addition to building upon GENIUS I drug targets and leads, we leverage recent innovative advancements to identify new druggable targets within male and female atherosclerotic lesions, as well as in circulating cells. State-of-the-art molecular biology techniques, including single cell sequencing and immunophenotyping, are actively employed to dissect immunometabolic processes within atherosclerotic plaques and patients. These studies will enable us to monitor the presence of drug targets at disease sites, expediting drug design and potentially identifying gender-specific biomarkers to aid disease progression monitoring and diagnosis. Subsequent studies involve testing the efficacy of small molecules, monoclonal antibodies, and siRNA against pre-selected targets from GENIUS I. We have identified small molecules and monoclonal antibodies for five targets, which will undergo toxicity and proof-of-pharmacology studies to progress towards drug development for cardiovascular patients. We have also identified three drugs affecting primary targets from GENIUS I and are assessing their potential to reduce atherosclerotic parameters in First-In-Human clinical trials. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation. The GENIUS II consortium builds on the most promising targets identified in the GENIUS I consortium, with the goal of advancing these targets towards clinical application.

Heart failure poses a large burden on patients and healthcare, largely because heart failure patients have low fitness and require frequent hospitalisation for close monitoring. In CardiacCare@Home, researchers work together with patients, doctors, industry, and others to develop technology for home-based monitoring of cardiac function and rehabilitation. This approach facilitates early detection of worsening of cardiac function, which allows doctors to rapidly alter treatment and prevent hospitalisation. Moreover, home-based rehabilitation will improve patients’ fitness levels. Technological innovations will facilitate a new care path that improves patients’ quality of life and lower socio-economic costs, and lower burden for hospital staff. The research CardiacCare@Home has the following aims: To integrate a feasible, easy-to-use monitoring + biomarker system within the home environment of patients with HF, that is validated against gold standard measures, and to identify parameters suitable for integrated, frequent patient evaluation to improve and personalise treatment. To design an inclusive transmural home-based cardiac rehabilitation programme, personalised to patient (and caregivers) and disease characteristics, tailored to the needs and preferences and co-created with relevant end-users using a combination of user-friendly sensors and an eHealth platform. To develop a data analytics and decision support system to be incorporated in a novel eHealth platform to (i) enable effective monitoring of vital signs for the personalised, early detection of clinical deterioration, and (ii) facilitate personalised behaviour change to improve participation in rehabilitation. Co-develop an integrated, AI-driven, home-based monitoring and/or home-based rehabilitation program in patients with chronic HF after hospital admission due to decompensated HF, and assess its effects on quality of life, functional capacity and re-hospitalisation (WP3). To assess the impact, including cost-effectiveness and budget impact, of the home-based monitoring and/or rehabilitation CardiacCare@Home-intervention compared to current care from the perspective of patients with HF, healthcare providers, health insurance companies, and society. The origin Heart failure is linked to poor hospital recovery, low functional capacity, and high risk of hospital re-admission. CardiacCare@Home aims to develop and adopt innovative technology for home-based monitoring and cardiac telerehabilitation to improve quality of life, reduce admission and lower healthcare costs. This project was funded by the NWO perspective TTW. This public-private program stimulates the development of innovative technologies that may impact economy and society.