Pulmonary arterial hypertension (PAH), or severe high blood pressure in the lung arteries, is a rare disease affecting some 6000 people in the UK. Sadly, despite existing treatments PAH is life-limiting.
Studies published 15 years ago determined that heterozygous mutations in the gene encoding the bone morphogenetic protein type II receptor (BMPR-II) are the most common genetic cause of the disease.
Now, Professor Nick Morrell and colleagues (Medicine) have determined that a particular circulating bone morphogenetic protein (BMP9) is the preferred ligand for the BMPR-II receptor complex on endothelial cells. They showed that BMP9 stabilises and protects the endothelial lining in the lung arteries. Excitingly, BMP9 therapy reversed established disease in several rodent models of PAH.
The research, published in Nature Medicine provides a novel approach to treating this devastating condition, which for the first time targets the critical pathway identified from human genetic studies. The team are planning experimental studies in patients within the next 2-3 years.