New therapeutic strategies for Marfan and other genetically-triggered aortic aneurysm syndromes

A faulty gene weakens the walls of the aorta—the body’s largest artery—and can trigger a sudden, catastrophic rupture with no warning. This project aims to find the first drug treatments to prevent that. Currently, patients with Marfan syndrome and related genetic conditions have no specific medicines to stop their aortas from ballooning and tearing. Surgeons can replace the damaged section, but only after it has already become dangerously enlarged. The underlying molecular chain reaction that kills the smooth muscle cells in the vessel wall remains poorly understood. The researchers have built a human stem-cell model of Marfan syndrome in a dish that mimics the aneurysm’s behaviour. They have already identified one signalling molecule, p38 MAP kinase, that drives cell death in the most vulnerable part of the aorta. Now they will use this model—alongside mouse models—to map the common pathways across several aneurysm syndromes and test potential drugs. If this works, the impact would be a shift from watching and waiting for a rupture to prescribing a therapy that stabilises the aortic wall. That could turn a life-threatening condition into a manageable chronic one.