Molecular and cellular causes of mitral valve prolapse

Project: Research


  • Russell Norris (PI)


Cardiac valve disease is a major health burden. Mitral valve prolapse (MVP) is one of the most common forms of cardiac valve disease and affects ~2-3% of the human population. While surgical techniques continue to improve, the number of surgical cases and associated mortality rates are increasing. In fact, surgeries for degenerative mitral valve disease increased more than 44% from 2011-2016 and, to date, >90,000 mitral valve surgeries occur each year making it the fastest growing cardiovascular intervention in the United States. MVP carries a significant burden of morbidity and mortality with secondary complications (e.g. arrhythmia, fibrosis, heart failure and sudden cardiac death). Currently there are no effective nonsurgical treatments. A critical barrier to developing new treatments is the lack of understanding for how MVP begins and progresses. Significant in-roads towards understanding disease causes were recently uncovered by our group. These studies led to the first genetic discoveries for non-syndromic MVP in familial and population studies and revealed dysregulated primary cilia biogenesis and function as mechanisms underlying disease causation. Consistent with the mission of the AHA Transformational Project Award (TPA) this project will build on our successful initial studies in a second phase of research with the goal of defining how cilia are built and the downstream consequences of their perturbation. Two specific aims are proposed that test hypotheses underlying cilia biogenesis (Aim 1) and cilia function (Aim 2) with the overall goal of defining how dysregulated cilia can cause MVP and whether the pathways identified during the course of study can be therapeutically targeted for patient benefit.
Award amount$300,000.00
Award date07/01/2019
Program typeTransformational Project Award
Award ID19TPA34850095
Effective start/end date07/01/201906/30/2022