DEFENCE

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.

Clinical staff in hospital wards traditionally collect vital signs periodically to assess a patient's cardiorespiratory status, often with intervals of 6 to 10 hours. This method, known as spot-checking, has limitations due to its infrequent nature and dependence on contact sensors, which can be uncomfortable for patients, particularly during sleep. The Focus Recent advancements demonstrate that vital signs like heart rate, respiration rate, blood oxygen saturation, and temperature can be monitored remotely using camera-based methods, which are less invasive compared to contact sensors. This innovation could significantly enhance patient comfort by enabling continuous monitoring without the need for frequent interventions by clinical staff. Continuous monitoring also allows for trend analysis of vital signs, offering a comprehensive assessment of a patient's cardiorespiratory condition. Additionally, camera-based methods enable video context analysis, such as detecting patient movements or identifying pain through facial expression analysis. This project explores the use of continuous video monitoring as an unobtrusive method to predict and monitor patient deterioration or adverse events. The Research Initially, the feasibility and reliability of camera-based continuous monitoring will be evaluated using data from consenting patients in the ICU at Catharina Hospital in Eindhoven and healthy volunteers. Subsequently, robust technologies will be developed to automatically detect signs of patient deterioration by generating automated early warning scores based on measured vital signs. Throughout the project, feedback from clinical staff and patient experiences will inform the design and implementation of camera-based technologies and early warning systems. Origin This project is funded within the Innovative Medical Devices Initiative (IMDI) program 'Heart for Sustainable Care'. The focus of this program is the development of medical technology for the earlier detection, monitoring, and better treatment of cardiovascular diseases to ensure accessible healthcare and sufficient staffing. The program has been developed en funded by the Dutch Heart Foundation, ZonMw and NWO, who collaborate within the Dutch CardioVascular Alliance.