THR-123, a novel BMP-7 mimetic that activates Akt phosphorylation and inhibits cardiomyocyte apoptosis and inflammation, protects the heart from myocardial injury in a Rat model.

Acute myocardial infarction (AMI) continues to be the most common cause of heart failure despite the advancements in the treatment of Myocardial Infarction (MI) over the past 20 years. We have developed "BMP mimetics" that selectively activate the BMP signaling pathway, and do not induce bone formation. A BMP-7 mimetic, THR-123, is anti-inflammatory, anti-apoptotic, anti-fibrotic and promotes tissue regeneration. In an animal model of ischemia-reperfusion using LAD coronary occlusion-induced myocardial injury, THR-123 markedly decreased myocardial infarct size (84%) and pericardial inflammation. The mechanism of action of THR-123 was examined in three different cellular (cardiomyocytes) models. Mechanistically, THR-123 activates Akt phosphorylation and inhibits inflammation and apoptosis in cardiomyocytes. These results show that the BMP-7 mimetic (THR-123) protects cardiomyocytes, and limits infarct size after myocardial ischemia and reperfusion injury. THR-123 may provide a novel pharmacological intervention in myocardial injury.