Abdominal Aortic Aneurysms

Abdominal Aortic Aneurysms (AAA) are a pathologic dilatation of the aorta, the main blood vessel from the heart, that leads to rupture and death if untreated.

AAA is the 13^th leading cause of death in the U.S. but its incidence is probably much higher as it has no symptoms until it ruptures. Of those patients who rupture half die before reaching the hospital, half will die after emergent surgery, so that ruptured AAA has a 70% mortality rate

Approximately 200,000 new AAA’s are diagnosed each year and surgical repair is indicated only when the AAA grows to a diameter of 5.5 cm. Thus many patients with smaller AAA’s must wait for years before repair and describe it as if having a ticking time bomb in their abdomen.

There are no current medical strategies to prevent or suppress AAA expansion and rupture to avoid surgery

At the ICVBM we are near completion of a Phase I clinical trial in which we are treating patients with small AAA with intra-venous infusions of mesenchymal stem cells obtained from a young healthy donor. Patients are randomized to placebo, low dose MSCs, and high dose MSCs. We have enrolled and treated 31 of 36 planned patients. Our preliminary results show a significant reduction of inflammatory cells that are related to AAA development and a significant increase in regulatory T cells that suppress inflammation, reaching the primary endpoint! More excitingly, using positron emission tomography[5] we have shown that MSCs decrease inflammation in the aorta in a dose-dependent fashion and prevent AAA from enlarging.

Based on these results we are designing a larger Phase II multi-center clinical trial.

Katherine Leckie, MD has demonstrated that that aortic aneurysms are a result of an auto-immune response to proteins in the aorta, specifically to a protein called elastin. Working with collaborators at Northwestern University we are using state of the art nanoparticle technology that will prevent patients from developing this immune response and prevent aneurysms from even starting.

Leckie has also invented a skin test that may identify patients at risk for AAA before the aneurysm actually develops. This will allow treatment to suppress aortic inflammation and prevent the AAA from starting.

We recently received a NIH grant with Teresa Zimmers, PhD focusing on muscle wasting and heart disease in patients with abdominal aortic aneurysms. We previously discovered that 50% of patients who had evidence of muscle wasting prior to surgical repair for their aneurysm died at 3 years. In the mouse models of aortic aneurysm, we have developed through Cryptic Masons funds we are testing our hypothesis that the chronic inflammation associated with aneurysm formation leads to heart failure.

[5] Positron emission tomography is a type of scan that can measure inflammation.