Compositions and Methods for Treating Pulmonary Hypertension
- Intravenous administration of daunorubicin is an FDA-approved drug for the treatment of oncologic malignanciesDaunorubicin induces cell death and suppresses pulmonary artery constriction in a hypoxia-induced animal model of pulmonary hypertensionDaunorubicin mediated suppression of pulmonary artery constriction reduces right heart blood pressure and hypertrophyLow dose daunorubicin as well as coadministration of the cardioprotectants Dexrazoxane and the p53 inhibitor Pilfithrin-α suppress cardiotoxic side effects associated with anthracycline treatment
- Pulmonary hypertension is a devastating disease currently without cure. Constriction of the pulmonary arteries strains the right ventricle of the heart which eventually leads to heart failure. Current therapeutics such as vasodilators suppress the symptoms of pulmonary hypertension but do not target an underlying cause of disease which is the expansion of pulmonary vascular cells. This invention describes a novel use for anthracyclines such as daunorubicin to treat pulmonary hypertension. The invention also describes the use of anthracylines in combination with cardioprotectants.
- “Pulmonary Hypertension-Induced GATA4 Activation in the Right Ventricle” Park AM et. al., Hypertension 2010; 56; 1145-1151“Anthracycline-Induced Suppression of GATA-4 Transcription Factor: Implication in the Regulation of Cardiac Myocyte Apoptosis” Kim Y et. al., Mol Pharmacol 63: 368–377, 2003
- *Stage of Development
- Daunorubicin has been demonstrated to kill pulmonary artery smooth muscle cells in vitro, and reduce vascular thickening in an animal model of pulmonary hypertension without causing a reduction in animal body weight.