The GENIUS II (Generating the best evidence-based pharmaceutical targets and drugs for atherosclerosis) consortium is focusing on atherosclerosis, the main underlying pathology of cardiovascular diseases. The main goal of the consortium is to translate druggable targets identified for the intervention in atherosclerosis into a clinical application.
As such, GENIUS II builds on the unique integration of knowledge within the consortium on dyslipidemia and the immune response related to dyslipidemia. Our work is divided into distinct work packages that represent the logical steps in drug development and accordingly each of the selected targets from GENIUS I to be studied is carefully placed into this track. Our investigations range from in vitro to in vivo analyses to improve mechanistic insight and druggability, and test effects on atherosclerosis. Next to directly building on GENIUS I drug targets and drug leads, we also take advantage of the most recent innovative developments to find new druggable targets in cells of male and female atherosclerotic lesions as well as in circulating cells. Recent developments in the field of molecular biology such as single cell sequencing and immunophenotyping of cells are actively used to dissect the immunometabolic processes within the atherosclerotic plaque and the atherosclerotic patients. These studies will create a platform in which we can monitor the actual presence of drug targets at the site of disease, which will speed up drug design. This is also expected to lead to the identification of novel gender specific biomarkers that can facilitate identification of disease progression and improve diagnosis. Subsequent studies will include the actual testing of the effectiveness of small molecules, monoclonal antibodies and siRNA that modulate pre-selected targets obtained in GENIUS I. For five targets we already defined small molecules and a monoclonal that affects these targets. The drug leads will be further translated along toxicity studies and proof-of-pharmacology studies into drugs ready to test in cardiovascular patients. We identified three drugs affecting the current foremost targets of GENIUS I and we study whether they can be efficiently applied to reduce atherosclerotic parameters in First-In-Human clinical studies. In all studies, we do address gender specificity. The talent program in our consortium is designed in such a way that all young talent working on GENIUS II will gain insight in the opportunities and challenges of developing drugs for cardiovascular disease.
Overall, GENIUS II focuses on translating knowledge towards a clinical application.