Variation in Platelet Function Could Hold Key to Drug Development and Predictors of Disease Risk

Newswise — Scientists at Jefferson Medical College have received a four-year, $3 million National Institutes of Health grant funded by the National Heart, Lung and Blood Institute to study variations of platelet function, specifically, the genetics of platelet gene expression. The study aims to find data that can be translated into novel therapeutic strategies and develop better predictors of cardiovascular disease. “This study is at the leading-edge of platelet genetic research,” said principal investigator Paul F. Bray, M.D., the Thomas Drake Martinez Cardeza Professor of Medicine and director, Division of Hematology in the Department of Medicine at Jefferson Medical College of Thomas Jefferson University. “We still have a limited understanding of the control mechanisms regulating platelet gene expression. Some patients have hyper-functioning platelets which can lead to strokes and heart attacks. On the other end of the spectrum there are some patients with bleeding disorders because their platelets don’t clot well enough. Thus, we are talking about very common clinical problems affecting huge numbers of people. We are hoping to shed some light on how the balance gets tipped from health to disease via changes in these fascinating and complex blood cells.” The study will focus primarily on looking at platelet microRNA. MicroRNA’s modify gene expression in all tissues, but little is known about how they function in platelets.

“We believe microRNAs serve as a rheostat for protein synthesis in platelets,” said Bray. “There are thousands of different settings. People who suffer clotting problems may have different levels of platelet microRNAs than do healthy people. We are going to study platelet microRNAs from healthy individuals and determine how these levels correlate with platelet function. Once we know the situation in healthy subjects, we can assess the critical microRNA levels in patients with unhealthy platelet function. This may serve as a biomarker to predict who might be at risk for bleeding or clotting in different clinical settings and to predict who may benefit from specific drug therapies.”

The study will be conducted at two centers: Thomas Jefferson University and Baylor-College of Medicine in Houston. 180 healthy patients over the age of 18 will be selected and prescreened for any potential drug interaction that may skew the results.

“This is a little different from traditional clinical studies in that we are looking for healthy, medication-free patients,” said Bray. “Invariably hospitalized patients are receiving multiple medications that may alter platelet function and distort the results. Therefore, we will do extensive pre-enrollment screening. Fortunately, it is fairly easy to find large numbers of eligible volunteers at large medical centers like Jefferson and Baylor College of Medicine.”

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