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.
