Baylor College of Medicine may have a new way to treat the rare lung disease lymphangioleiomyomatosis (LAM), which affects only women. LAM is usually concurrent with another rare genetic disease known as tuberous sclerosis complex (TSC), which causes tumors in the brain, kidneys, heart, eyes, lung, and skin. Since TSC impacts the central nervous symptom, patients have developmental delay, behavior problems, and seizures. Thirty five percent of women with TSC have LAM, and the symptoms of LAM include pneumothorax, chylous effusions (fluid leakage in the chest cavity), shortness of breath, and respiratory failure because LAM causes tumor-like growths that progressively destroy lung tissue.
Until the recent study from BCM was conducted and published in Cancer Research, it was a mystery as to where the proliferating tumor cells originate and how they become activated. “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,” said Dr. N. Tony Eissa, a professor at BCM. He recognized that the cells are invasive and move quickly, leading him to hypothesize that Src kinase might be involved. Src kinase is involved in the epithelial-to-mesenchymal transition and produces more mobile cells; it also plays a role in tumor development.
Together with Dr. Alexey Tyryshkin, a postdoctoral fellow, Dr. Eissa studied tissue from the lungs of healthy and LAM-afflicted people and animals to investigate the hypothesis that Src kinase is hyperactive in LAM tissues. Their study led to three main findings. First, Src kinase is activate in LAM cells. Second, it is intimately related to destructive LAM cells by promoting the cells’ mobile mesenchymal phenotype. Finally, inhibiting Src kinase reduces the potential of migration of LAM cells to the lungs in animals.
The last finding is promising for finding a drug treatment–Src kinase inhibitors are being developed that can inhibit Src kinase in cells. Dr. Eissa and colleagues are using some of these drugs in their current research and have found that the drugs can modulate the activity of LAM cells in vitro in tissue culture and in vivo in a mouse model of LAM. “The LAM cells are less likely to colonize the lung when treated with these drugs,” said Dr. Eissa.
Soon, human testing with the drugs will be conducted. “As a physician scientist, one of the most satisfying times is when you can move a study at the bench into the clinic,” said Dr. Eissa. “It is exciting for us to do clinical trials based on the work we have done in the laboratories.” Although there are current treatments for LAM, not all patients respond, and there is certainly no cure for LAM.