Bone morphogenetic protein 9 (BMP9) is a protein that is normally produced in the liver and circulates in the blood to maintain the integrity of cells, known as endothelial cells, which line the inner surfaces of blood vessels. Circulating BMP9 protects the endothelium and maintains vascular integrity and health.
In certain conditions, exemplified by idiopathic and heritable pulmonary arterial hypertension (PAH), levels of BMP9 are insufficient to protect the endothelium. Supplementation of BMP9 levels has been shown to prevent and reverse PAH in preclinical models of disease.
Morphogen-IX has successfully developed BMP9-based molecules that retain the protective benefits of native BMP9, but are devoid of the potential bone-forming effects of the native protein. The modifications to develop therapeutic BMP9-based proteins were made possible through an in-depth knowledge of the structural biology of the interactions between BMP9 and its receptors.
A panel of candidate molecules has been extensively evaluated in preclinical models. In 2018 a development candidate will enter a formal programme of studies that will support regulatory approval for a first-time-in-human clinical trial.
Control rat lung with normal small pulmonary arteries stained brown (smooth muscle actin)
Lung histology of a rat with severe PAH induced by Sugen-hypoxia, showing severe remodelling of small pulmonary arteries
Lung histology of a rat treated with BMP9 showing complete reversal of PAH induced by Sugen-hypoxia