Finding a cure for aortic stenosis

Aortic stenosis is the commonest valvular heart disease in the western world. Although it is inevitably fatal if left untreated, there are currently no medical treatments that can prevent, halt, or delay the disease. Even after procedural valve intervention, problems remain including subsequent bioprosthetic valve degeneration. Our approach will be to apply experimental medicine approaches to define the pathogenesis and disease progression of aortic stenosis and bioprosthetic valve degeneration. We will achieve this in 3 complementary and synergistic ways: discovery human pathobiology, monitoring of in vivo disease progression, and preliminary proof-of-concept experimental medicine studies. We will exploit innovative approaches to study explanted human and bioprosthetic tissue and to develop non-invasive molecular imaging of the aortic valve. We will establish a longitudinal cohort platform study that will repeatedly phenotype patients with aortic stenosis across the life course of their disease using advanced multimodal imaging and disease biomarkers. We will undertake exploratory proof-of-concept experimental medicine studies to identify leading targets that can be subsequently progressed to phase 2 clinical interventional trials to achieve our goal of finding the first medical therapy to treat aortic stenosis and bioprosthetic valve degeneration.