Cardiovascular disease is the single largest cause of death and disability worldwide; half of all patients with heart failure die within 5 years of diagnosis. The mineralocorticoid receptor (MR), is an established therapeutic target in heart failure. However, while current MR-blocking drugs (MRA) improve heart failure they can cause a deadly rise in potassium levels in the blood due to MR blockade in the kidney. Thus, many patients cannot benefit from these drugs. We showed that MR activation in heart/immune cells promotes cardiac disease. We therefore propose that a novel MR blocking drug with a selective mode of action will protect the heart but spare the kidneys. We developed three series of novel MRA, of which several show selective activity in heart cells and are potentially capable of eliminating the kidney side-effects. We will test these compounds in 2 animal models including heart disease with renal dysfunction to demonstrate that they work in vivo. This is the critical step before testing in humans and initiating clinical trials.
Last updated17 January 2023