A systematic approach to identifying and testing novel therapeutic targets for atrial fibrillation (renewal)

Atrial fibrillation patients currently have no treatment that alters the disease's progression or improves survival beyond stroke prevention. This matters because atrial fibrillation is a rapidly growing public health problem worldwide. The fundamental gap is that doctors can manage symptoms and prevent clots, but cannot stop the underlying heart damage that drives the condition. The researchers have already discovered that two proteins—nNOS and dystrophin—are depleted in the fibrillating human heart, and that a molecule called tetrahydrobiopterin affects heart energy use. Now they plan to test interventions in mice, large animals, and eventually patients that correct the heart tissue abnormalities that trigger or worsen atrial fibrillation. If this succeeds, it could produce the first therapies that actually change the natural history of atrial fibrillation—preventing its onset or halting the damage it causes to the heart muscle. That would mean fewer hospitalisations, less progression to permanent fibrillation, and potentially better survival for millions of people. The project also applies high-throughput gene analysis to a large biobank of human atrial tissue from the STICS trial, searching for molecular signatures that predict who will develop atrial fibrillation. This fundamental discovery work could reveal entirely new targets for early intervention.