Project leader: Virendar Kaushik, Ph.D.
Key collaborators: Kiran Musunuru, M.D., Ph.D., M.P.H.

Recent research shows that the PCSK9 gene regulates cholesterol levels in the blood, and is one of the key genes that drives elevated levels of LDL cholesterol. A therapy that successfully targets the PCSK9 protein and modulates LDL cholesterol would transform the treatment of coronary artery disease, one of the leading causes of death worldwide.

While many heart disease patients take statins in order to lower LDL cholesterol, these drugs can cause side effects. And although injectable antibodies are in clinical trials to target the PCSK9 protein, the need for frequent shots and the potential duration of action pose potential obstacles.

To gain a comprehensive understanding of the biology of the PCSK9 pathway, and develop small molecule therapies, Broad scientists are leveraging high-throughput screening of a unique collection of 110,000 small molecules against this traditionally “undruggable” target.