Novel Therapeutic Target for Rare Lung Disease Discovered

April 3, 2014
Rachel Lutz

Inhibiting an enzyme called Src kinase may be a potential new treatment for a rare lung disease known as lymphangioleiomyomatosis.

An enzyme called Src kinase may serve as an activator in a rare women’s lung disease known as lymphangioleiomyomatosis (LAM), according to a study published in Cancer Research.

LAM appears in women either alone or in conjunction with tuberous sclerosis complex (TSC), a genetic disorder that affects many organ systems in the human body. Women with TSC can develop a variety of tumors in the brain, kidneys, heart, eyes, lungs, and skin, as well as suffer seizures, developmental delay, behavior problems, skin abnormalities, and kidney disease. Although LAM is found in 35% of women with TSC, the condition can also sporadically develop due to related genetic mutations.

LAM causes women to develop lung lesions that destroy lung tissue. This progressive cystic lung disease is associated with collapsed lung, chylous effusions, shortness of breath during exercise, and respiratory failure.

To learn more about Src kinase’s role in tumors and its activation of epithelial cells to transition into mesenchymal cells, researchers from Baylor College of Medicine studied lung tissue from healthy individuals, LAM patients, and animal models. They discovered Src kinase is activated in LAM cells and subsequently activates mesenchyal cells to become more mobile and invasive. The researchers also found that by inhibiting Src kinase with drugs, the potential of LAM cells to migrate into the lungs decreased in animal models. Conversely, increased Src kinase activation promoted migration and invasion.

“We had come to the point where people were beginning to think that these cells that destroy lung tissues might actually come from a place outside the lung,” N. Tony Eissa, MD, professor of medicine — pulmonology, pathology, & immunology and molecular and cell biology, said in a statement. “The LAM cells are less likely to colonize the lung when treated with these drugs.”

The researchers said their next steps will involve testing the novel therapeutic target drugs in subjects with LAM. Currently, there are existing treatments for LAM, but not all patients respond well to them.