Activation of AMPK to treat abdominal aortic aneurysm (5As). (Old ID 31075)
Role
Chief Investigator
Description
Twenty million people worldwide (100,000 Australians) have weakening and dilatation of their main abdominal artery (AAA), responsible for 200,000 deaths/year due to aneurysm rupture. Randomised controlled trials show that surgery does not benefit patients with aneurysms <55mm in diameter. About 95% of AAAs are identified when they are small and are simply imaged every 6 to 12 months until aortic diameter becomes ≥55mm, when surgery is considered. About 5% of AAAs fatally rupture during surveillance and 70% grow within 5 years to 55mm and are repaired, with the risk of complications. The lack of treatment for small AAA concerns patients who worry about aneurysm rupture, which impairs their quality of life. Surveys of patients and specialists, and our systematic reviews show the number one deficiency in AAA management is the lack of drugs to prevent aneurysm growth and rupture. A wealth of evidence suggests that pharmacological activation of the AMPK pathway may prevent AAA growth and rupture. We have access to a novel potent 5′ adenosine monophosphate-activated protein kinase (AMPK) pathway activator (O304) which has been shown to be safe in older adults for other indications. This 5As project will build on our past discoveries using our unique resources and expertise (clinically-relevant mouse model, human AAA explant culture methods, novel drug, statistical methods, human AAA biobanks, registries and genome wide data) to test if: 1. AMPK agonist 0304 inhibits aneurysm growth and rupture in our mouse model; 2. AMPK agonist 0304 reduces markers of AAA growth in human AAA samples in vitro; 3. Genetic AMPK upregulation is protective against AAA development and growth.
Date
01 Feb 2024 - 31 Jan 2027
Project Type
GRANT
Keywords
Prevention;Complications;Peripheral artery disease;Risk factors
Funding Body
Commonwealth Department of Health
Amount
1044836
Project Team
Joseph Moxon;Norelle Daly;Jenna Graffini;Catherine Rush