Yale Cancer Center researchers at Yale School of Medicine are studying novel and innovative methods to treat von Willebrand disease (vWD), the most common bleeding disorder. It occurs due to the deficiency of a coagulation protein called von Willebrand factor (vWF). Senior author of the study Anish Sharda, MD, will present the new research at the American Society of Hematology (ASH) Annual Meeting in San Diego, Calif., on December 10.
“Von Willebrand disease is common but the current treatment options are limited, partly because our understanding of how vWF, which is so critical for normal blood coagulation, is stored in the vascular lining of cells and is ultimately secreted at the site of vascular injury,” said Dr. Sharda, Yale Cancer Center member and assistant professor of medicine (hematology) at Yale School of Medicine.
In the study, the research team looked at how RalB — an important cellular protein that functions as a molecular switch — affects vWF secretion from its sources in the circulation. They found out that RalB was essential for vWF to come out of the cell and into circulation. In this process, RalB interacted with another protein, the exocyst, which anchored vWF storage granules to the cell membrane. Disrupting this interaction between RalB and exocyst increased vWF secretion significantly – nearly a 40% increase from baseline.
Researchers believe their findings could have substantial implications in the treatment of vWD, but also cardiovascular disease and other pathophysiologic processes such as cancer metastasis and the formation of healthy, new blood vessels (angiogenesis).
“We are excited that our research data are being recognized as important by the American Society of Hematology, and we hope to closely translate these results in the clinic in the coming years,” said Dr. Sharda, who treats patients through the Smilow Cancer Hospital Classical Hematology Program.