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Tufts Medical Center researchers receive $10 million NIH grant to test blood clot prevention drug

Boston, Mass. (July 3, 2012) Tufts Medical Center researchers are developing a first-of-its-kind drug to prevent deadly blood clots in heart disease patients, without the risk of serious bleeding associated with current medications. The National Heart, Lung, and Blood Institute of the National Institutes of Health has just awarded the team led by Athan Kuliopulos, MD, PhD, a $10 million grant to start testing a drug based on this novel technology.

"If our study works, it's potentially game-changing and could become part of the standard of care for patients being treated for coronary artery blockages," said Kuliopulos, Director of the Hemostasis and Thrombosis Lab at Tufts Medical Center.

Heart disease is the leading cause of death in the United States. The new approach could benefit patients who have had heart attacks or who need cardiac catheterization procedures to prop open clogged arteries with a stent. These patients face increased risk for blood clots that can cause heart attack and death. To reduce these risks, patients are currently treated with anti-clotting drugs, which increase their risk of life-threatening bleeding problems.

In a study to be published today in the journal Circulation, Tufts Medical Center researchers have discovered a mechanism to inhibit the ability of platelets to form clots without increasing the risk of bleeding. The new approach uses pepducins, which are able to travel inside cells to block receptors and inhibit molecular pathways that stimulate clot formation. By contrast, most approved drugs block receptors on the outside of cells. If successful, this new strategy could lead to an entirely new class of drugs.

The pepducin, PZ-128, inhibits PAR1, a platelet protein that stimulates clotting. When added to human blood samples, PZ-128 appears to inhibit clotting without affecting bleeding markers. It also clears out of the blood stream within hours, which should reduce the risk of long-term bleeding problems.

"Anytime you have a new molecule that exploits a novel mechanism of action, it's very exciting and the benefit to patients is potentially tremendous,'' said Carey Kimmelstiel, MD, Director of the Cardiac Catheterization Laboratory and Interventional Cardiology at Tufts Medical Center. "A new technology that can inhibit platelet function without increasing bleeding would be enormously powerful."

The next step is to evaluate the safety and effectiveness of the pepducin in humans. The five-year, $10 million NIH grant will fund the early stages of drug development. Researchers will first conduct a Phase I clinical trial in healthy human volunteers to determine whether the drug is safe. If successful, the grant will cover a multi-center Phase II clinical trial in 800 patients.

The research is the result of a long-term collaborative effort between laboratory scientists and the clinicians in the Cardiac Catheterization Laboratory at Tufts Medical Center.

"These exciting advances would not have been possible without this strong partnership," said Kuliopulos. "It is critical for researchers to have an understanding and appreciation of the clinical issues and practical matters concerning the real-world application of the drug."


Contact: Julie Jette
Tufts Medical Center

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