Developing BMP9 as a new therapy for pulmonary hypertension

Development of non-osteogenic variants of bone morphogenetic protein 9 as novel therapies for pulmonary arterial hypertension

Dr Wei Li and her team are looking for ways to treat pulmonary arterial hypertension (PAH), a serious condition where people have high blood pressure in the arteries of the lungs. Current therapies relieve the symptoms but do not cure the disease, so many people still die within a few years of diagnosis. BMP9 is a protein that circulates in the blood and binds to endothelial cells lining the blood vessels, activating protective signalling pathways in these cells. Dr Li and her team have found that BMP9 can cure PAH in animals with the disease. This is particularly exciting because faults in the BMP9 gene cause PAH in people. But giving BMP9 to treat PAH has a serious drawback - it causes bone to form in muscle. In this project, Dr Li will generate and test altered forms of BMP9 that cannot form bone, but that still retain the ability to reverse PAH. So far, the team has modified the surface of the BMP9 protein and generated eight BMP9 variants with no bone-forming activity. They will now carry out several tests on these BMP9 variants and get them ready to use in clinical studies. This research is a first step in the research needed to move BMP9-based therapy to the clinic, where it could greatly benefit people with PAH.