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The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension.
Human genetic discoveries offer a powerful method to implicate pathways of major importance to disease pathobiology and hence provide targets for pharmacological intervention. The genetics of pulmonary arterial hypertension (PAH) strongly implicates loss-of-function of the bone morphogenetic protein type II receptor (BMPR-II) signalling pathway and moreover implicates the endothelial cell as a central cell type involved in disease initiation. We and others have described several approaches to restore BMPR-II function in genetic and non-genetic forms of PAH. Of these, supplementation of endothelial BMP9/10 signalling with exogenous recombinant ligand has been shown to hold considerable promise as a novel large molecule biopharmaceutical therapy. Here, we describe the mechanism of action and discuss potential additional effects of BMP ligand therapy.
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