A compound that mops up debris of damaged cells from the bloodstream may be the first in a new class of drugs designed to address one of medicine's most difficult challenges -- stopping the formation of blood clots without triggering equally threatening bleeding.
In a mouse study published online July 23, 2012, in the journal Proceedings of the National Academy of Sciences, Duke University Medical Center scientists report that the experimental compound called PAMAM G-3 actually prevents activation of the process that leads to the formation of dangerous blood clots, while avoiding any impact on the factors that are essential to normal blood clot formation.
"In the thrombosis (clotting) space, the holy grail has been to make something anti-thrombotic that doesn't significantly increase your chance of hemorrhage or bleeding," said Bruce A. Sullenger, Ph.D., director of the Duke Translational Research Institute and senior author of the study. "We think this is a promising example of a type of compound that could do that. If it can be clinically developed and exhibit the same properties in humans, clearly that would improve safety and outcome of treating patients who have thrombotic disease."
Thrombosis, the formation of blood clots in the circulatory system that form blockages, is a major cause of death in the Western world, contributing to the mortality associated with leading killers such as myocardial infarctions, stroke, and even cancer.
"If you can control thrombosis without greatly increasing hemorrhage or bleeding risk, you would address a major unmet medical need," Sullenger said. "It would have potentially major clinical implications."
The thrombosis study builds upon previous work by Sullenger and his group, which showed that the compounds called nucleic acid-binding polymers or NABPs, which include PAMAM G-3, have potent anti-inflammatory properties. Work published last year by Sullenger's lab demonstrated the polymer's potential to interrupt the inflammatory response that is the hallmark of auto-immune disorders such as lupus and multiple sclerosis.