Scientists Restore Lost Protein BMP3 to Reverse Pulmonary Arterial Hypertension in Preclinical Models
Key Insights
Researchers at Virginia Tech's Fralin Biomedical Research Institute identified BMP3 as a natural protective protein that maintains healthy lung blood vessels and is significantly reduced in pulmonary arterial hypertension (search).
Two therapeutic strategies—recombinant BMP3 protein and lung-targeted gene therapy—both reversed key disease features including pulmonary vascular remodeling and heart dysfunction in preclinical models.
Circulating BMP3 levels were consistently lower in PAH patients, suggesting potential utility as both a therapeutic target and a disease-monitoring biomarker.
Researchers at the Fralin Biomedical Research Institute at VTC (search) have discovered that restoring levels of a naturally occurring protective protein can reverse key features of pulmonary arterial hypertension (search) (PAH), a rare and progressive disease that causes elevated blood pressure in the lungs and can lead to heart failure. The findings, published in the European Respiratory Journal, identify bone morphogenetic protein 3 (search) (BMP3) as a previously unrecognized player in PAH and open two distinct therapeutic paths forward.
"Pulmonary arterial hypertension (search) remains a devastating disease with limited treatment options," said Yassine Sassi, senior author of the study and an associate professor at Virginia Tech's Fralin Biomedical Research Institute. "Most current therapies focus on managing symptoms or slowing disease progression. What makes this discovery exciting is that it identifies a new therapeutic strategy aimed at restoring a natural protective mechanism that is lost during disease."
A Protective Signal Lost in Disease
The research team discovered that BMP3 is produced by cells in the walls of lung blood vessels. In healthy lungs, BMP3 helps keep blood vessel cells from growing and spreading too aggressively. However, in pulmonary arterial hypertension (search), BMP3 levels fall dramatically. Without sufficient BMP3, blood vessels begin to thicken and narrow, restricting blood flow through the lungs.
The study found that BMP3 levels were consistently reduced in lung tissue and blood samples from patients with pulmonary arterial hypertension (search), as well as in experimental models of the disease. Although BMP3 has been studied previously in bone biology and cancer, this study is the first to identify a role for the protein in pulmonary arterial hypertension.
Dual Therapeutic Strategies Show Promise
To test whether restoring BMP3 could counteract disease progression, the researchers employed two different methods. The first approach used recombinant BMP3 protein, while the second utilized a lung-targeted gene therapy designed to increase BMP3 expression. Both strategies significantly reduced disease severity in multiple preclinical models, improving pulmonary vascular structure and cardiac function.
"This gives us two potential therapeutic paths forward: a biologic therapy and a gene-based approach, both designed to restore a natural protective signal that is lost during disease," said Sassi, who is also an associate professor with the Virginia-Maryland College of Veterinary Medicine's Department of Biomedical Sciences and Pathobiology.
Biomarker Potential
Beyond its therapeutic implications, the team found that circulating BMP3 levels were significantly lower in patients with pulmonary arterial hypertension (search), suggesting the protein could eventually serve as both a therapeutic target and a biomarker for monitoring disease progression. By restoring BMP3 levels, researchers were able to suppress the cellular changes that drive disease progression and reverse key features of the disease in preclinical models.
A Path Toward Disease Reversal
The findings are particularly significant because no currently approved therapy for PAH reverses the underlying vascular remodeling that characterizes the disease. While additional studies are needed before the approach can be evaluated in patients, the research identifies BMP3 as a promising therapeutic target.
Sassi and first author Aymen Halouani of the Fralin Biomedical Research Institute have filed a patent application covering BMP3-based therapeutic approaches for pulmonary arterial hypertension (search).