Myocardial energetics in ischaemia and heart failure – exploring translational potential (renewal years 14-18)

The heart’s energy supply chain relies on a network of phosphate-transfer enzymes, and boosting one of them—creatine kinase—protects mice from heart attacks and heart failure. This matters because heart failure and ischaemia (restricted blood flow to the heart) remain leading causes of death, and current treatments do not directly address the energy deficit that drives them. The researchers have already shown that overexpressing creatine kinase in mice shields the heart from damage. Now they need to test whether that protection holds in more realistic scenarios: during cardiac surgery (when the heart is deliberately stopped with cardioplegia), in animals with common co-morbidities like diabetes, and in models of angina. They also plan to search for other proteins that regulate cardiac energy flow, using unbiased gene and protein screens, and to test new drug-like molecules they have developed. If this works, it could lead to entirely new classes of drugs that treat heart failure and protect the heart during surgery by fixing its energy supply, rather than just managing symptoms. The work is translational—it aims to move from mouse experiments toward human therapies—but remains at the preclinical stage.