Molecular guidance for calcific aortic valve disease treatment and management

Calcific aortic valve disease (CAVD) is the most common valve disease for which management is limited by unpredictable disease progression into severe aortic stenosis and the lack of medical treatments.

The objective of this project is to prioritize, validate, and translate key pathophysiological processes of CAVD for implementation as therapeutic targets and identification of classifiers for progression trajectories to guide CAVD management.

A five-step work plan with is proposed, consisting of (1) target prioritisation by tissue multi-omics of genetic targets and predefined pathways.

This is followed by (2) target validation through mechanistic in vitro cellular studies in valvular and immune cells, and in vivo CAVD models. (3) A target translation into clinical context will be performed through large scale cohorts multi-omics studies in relation to incident and prevalent CAVD and CAVD progression.

To deploy key CAVD pathophysiological processes, (4) targets will be integrated in an AI environment to pave way towards novel therapeutic options for druggable or available for repurposing of existing drugs, and identifiy predictors of fast CAVD progressors. (5) Target implementation will include of clinical trial design and personalized clinical CAVD surveillance based on predictors of CAVD progression trajectory.

The results of the project have the potential to respond to the unmet medical needs of CAVD, for which prevalence is expected to triple over the next three decades.