A new study done by researchers from Cincinnati Children’s Hospital Medical Center, and published recently in the journal Nature Communications talks about why air sacs in the lungs gets filled up with a thick substance called surfactant when one is suffering from a brutal disease known as Pulmonary Alveolar Proteinosis (PAP). The study also reports that effectively taking statins, which are cholesterol-busting pills, can help treat the disease.
The research team found out that it is actually cholesterol that leads to PAP. The research was led by Bruce Trapnell, who is the director of the Translational Pulmonary Science Center, and indicates that the PAP is linked to changes in cell regulation by a molecule known as granulocyte-macrophage colony stimulating factor (GM-CSF)- which plays a key role in the development of mature macrophage cells in the lungs. These macrophage cells are necessary for clearing away the used surfactant.
For the study, researchers worked with PAP patients and mouse models of the disease. The research team also discovered a more precise reason that disrupts cell regulation by GM-CSF which triggers PAP. The thing is, cell dysregulation significantly reduces the ability of the macrophages to process and clear out cholesterol. This actually leads to increase in the levels of cholesterol- which causes surfactant to accumulate which causes PAP and makes breathing problematic.
“Showing that the pathogenic driver of the disease is disruption of cholesterol homeostasis in these patients will change thinking in the PAP field,” adds Trapnell. “Now that we know cholesterol in macrophages is a target for therapeutic development, repurposing statins is a pretty straight forward pharmacological approach for treating people with PAP.”
The findings of the study might lead to a clinical trial to see if the statin therapy can also help larger number of patients with PAP. The current study involved with only two adult patients and genetically engineered mouse models of PAP.
Stain therapy helped improve cholesterol balance in pulmonary macrophage cells and also led to the surfactant clearing up from lung air sacs, in both human patients and animal models of PAP. This also improved the respiratory function in adult patients and in the laboratory models as well.