A new drug treatment to stabilise established abdominal aortic aneurysms

2020 Vanguard Grant

Years funded: 2021-2022

Abdominal aortic aneurysm (AAA) is an irreversible, asymptomatic condition where the abdominal aorta (main artery of the body) is weakened and dilated, eventually leading to rupture.  A high death rate of 50-80% is associated with this catastrophic event. Current standard of care for AAA patients involves monitoring aneurysm diameter, with surgery the only option when the aorta exceeds 55 mm in diameter. However, the majority of AAAs measure <55 mm and with no drug treatments available to stabilise or retard AAA development and progression, these patients are ticking time bombs.

Our exciting preliminary data revealed that mice treated with drugs that selectively block the activity of the enzyme insulin regulated aminopeptidase (IRAP), were protected against the development of AAA in a mouse model of the disease.  We also found that the level of IRAP is increased in the blood vessels in disease states. We propose that IRAP is a novel target that can be used to develop a completely new class of treatment for AAA.  In support of this, inhibiting IRAP with a novel drug that we have developed, alters many of the pathways involved in the development and progression of AAA.  This results in improved blood vessel function and prevention of AAA formation. Our findings give an early indication that we may be able to slow or even stabilise AAA progression in an animal model.

The current project will test the feasibility of preventing the development of, as well as stabilising and potentially reversing established aneurysms in an animal model of AAA using drugs that selectively block IRAP activity. Importantly we will also assess the potential use of measuring IRAP expression in blood from patients with and without AAA to determine if we can use this enzyme as a biomarker, making it easier to diagnose patients with asymptomatic AAA.