PREDICT 2

An aneurysm is a bulging or dilation of a blood vessel that usually causes no symptoms but can become life-threatening if it ruptures. It most commonly occurs in the body’s main artery (aorta) or in the brain arteries. Each year, thousands of people in the Netherlands are diagnosed with an aneurysm. The national initiative Aneurysm-NL brings together knowledge and research to improve diagnosis and treatment. By fostering collaboration between physicians, researchers, and patients, we aim to detect aneurysms earlier and treat them more safely, ultimately improving care and reducing mortality from this condition. The Research Aneurysm-NL aims to build a sustainable, nationwide infrastructure that connects medical centers, researchers, and patients to accelerate innovation in aneurysm research and care. A central focus is the development of a national data platform that integrates clinical records, imaging, biobank samples, and genetic information. This resource will allow researchers to reconstruct lifetime disease trajectories, improve risk prediction, and enable more personalized treatment. In parallel, the project develops advanced research tools, including patient-derived in vitro aneurysm models and large-scale omics-approaches to identify new therapeutic targets. By integrating clinical insights with computational modeling and real-world outcome data, Aneurysm-NL supports better decision-making and more effective interventions for both aortic and cerebral aneurysms. It also evaluates the safety and effectiveness of current endovascular and neurosurgical treatments for unruptured brain aneurysms through a large multicenter study. Aneurysm-NL also invests in building a strong and inclusive research community. The project emphasizes collaboration between researchers, clinicians, and patients, and actively works toward linking its infrastructure to national registries and existing healthcare data sources to ensure long-term sustainability and broad accessibility. By uniting expertise from across the country, Aneurysm-NL strives to generate new knowledge, enable earlier and more accurate diagnosis, and personalize treatment strategies for aneurysm patients. The Origin The Aneurysm-NL consortium was established following an exploratory initiative within the Dutch CardioVascular Alliance (DCVA), aimed at identifying opportunities for a national approach to aneurysm research. Based on this exploration, Barend Mees, Hanneke Takkenberg and Mervyn Vergouwen were appointed as coordinators to lead the formation of the consortium. Following a national call in April 2024, they brought together clinicians, researchers and patients from across the Netherlands to collaborate in this new initiative. With funding from the Dutch Heart Foundation, Aneurysm-NL now aims to grow into a nationwide network and data infrastructure, uniting clinical and scientific expertise to advance aneurysm research and care in the coming years.

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.