Grant: Operating Grant

Abdominal aortic aneurysm (AAA) is a disease that occurs in the main blood vessel (aorta) that supplies blood to the lower extremities. During AAA, weakening of the wall of the aorta causes it to balloon outwards. When the vessel expands to a certain point, it can rupture leading to abdominal bleeding. If not treated immediately, there is a 90% chance of death. AAA is a silent disease and rupture is often the first sign of disease. As such, AAA is the 13th leading cause of death in North America. Unfortunately, the only treatment for AAA is at later stages when the risk of dying from surgery outweighs the risk of rupture. There are no pharmacological treatments for small aneurysms. We have identified a protein degrading enzyme (GrB) that breaks down the proteins responsible for maintaining the structural integrity of the aorta wall. When this enzyme is blocked, AAA progression and rupture are reduced. The current proposal will determine how GrB attacks and weakens blood vessels and whether inhibitors targeted to this protein can prevent the disease from occurring or advancing further if the disease is already present. Due to early screening programs that have been implemented, it is expected that there will be increasing demand for new, non-surgical treatment options that can be used early after detection to prevent AAA growth and rupture. Such treatments would ultimately reduce both the patient's sense of helplessness and the need for surgery.