Only a few hundred cases of alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) have ever been identified or recorded. While there could, arguably, be more cases – especially considering potential misdiagnosis – researchers and scientists are still learning about ACDMPV and how it can be treated. Currently, the standard-of-care is lung transplantation; without this, ACDMPV is fatal within the first year of life. According to Medical XPress, however, a team of scientists from Cincinnati Children’s may have discovered a potential treatment option for this rare condition: a bone growth protein called BMP9.
To learn more about BMP9 and the study findings, take a look at the data published in Nature Communications.
Identifying BMP9 as a Potential Treatment
To begin their study, the research team first sourced over 7,000 lung cells from mice with ACDMPV-related genetic mutations (loss-of-function FOXF1), as well as 6,000 normal lung cells. Next, the team began identifying and isolating cell clusters which could potentially be related to this condition. Their searches evaluated myofibroblasts, club cells, alveolar epithelial cells, and more. Through this research, the team eventually focused on endothelial progenitor cells within microvascular blood vessels in the lungs.
Further research highlighted the role of a specific signaling pathway within this condition. FOXF1 gene mutations cause reduced ACVRL1 protein expression, preventing blood vessels in the lungs from developing properly. But when the researchers added BMP9, a bone growth protein found in the same signaling pathway, to cells, they saw a promising result. The BMP9 helped activate ACVRL1. This allowed for proper and effective capillary development, as well as increased oxygenation.
Right now, there are no approved BMP9 therapies. However, if more research shows the benefits of BMP9 for lung and blood vessel disorders, researchers could work towards creating and testing a therapeutic in the future.
About Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV)
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare congenital lung and blood vessel disorder. This condition results from FOXF1 gene mutations or chromosome 16 deletions. However, in some cases, the exact genetic cause of ACDMPV is unknown.
ACDMPV occurs when small alveolar blood vessels (capillaries) do not properly develop and are positioned improperly within the lungs. Additionally, pulmonary veins are positioned improperly and may be abnormally clustered. Ultimately, this prevents proper lung function and puts extra strain on the heart. Typically, symptoms appear within minutes to days following birth, though in rare cases, symptoms may not appear until a few weeks to months later. Symptoms include:
- Shortness of breath and/or difficulty breathing
- Cyanosis (bluish discoloration of the skin, lips, and nail beds)
- Pulmonary hypertension (high blood pressure in the lungs)
- Hypoxia (lack of oxygen in the blood stream)
- Large intestine malrotation or other intestinal defects
- Hydronephrosis (swelling of the kidneys due to urinary backup)
- Underdeveloped left side of the heart