In March, researchers from Temple University (TU) and the University of Delaware (UD) published results of a study in The Journal of Biological Chemistry explaining the mechanism the drug fucoidan uses to promote blood clotting. Fucoidan, a drug currently in clinical trials, is a carbohydrate (sulfated polysaccharide) derived from brown seaweed. The lead investigator of the study was Satya P. Kunapuli, PhD, director of TU’s Sol Sherry Thrombosis Research Center in Philadelphia.
Normally, platelets in the blood work cooperatively with a series of clotting factors to form a clot and reinforce it. However, in people with bleeding disorders the process is disrupted. “When a blood vessel is injured in a person with hemophilia, the platelets, the ‘policemen’ that are the first to respond, are fine, but some of the clotting factors are either missing or mutated,” explains Ulhas Naik, PhD, professor of biological sciences at UD and director of the Delaware Cardiovascular Research Center. He was a co-author of the study. “Without these clotting factors, the platelets can still form a plug to stop the bleeding, but it takes longer to build and is not as strong.”
Using mice, Kunapuli, Naik and colleagues confirmed that fucoidan works by activating platelets, not by replacing or stimulating specific clotting factors. The researchers discovered the mechanism it uses to accomplish this--the so-called “C-type lectin-like receptor 2 (CLEC-2).” Fucoidan binds to platelets via CLEC-2, activating them and enhancing their ability to form and retain clots. This pathway could offer an alternative to increasing particular factor levels through traditional factor replacement. Interestingly, snake venom also activates CLEC-2. A bite from a venomous snake triggers the enhanced platelet activity. The resulting clots that form help incapacitate the snake’s prey.
The authors warned investigators to avoid using the drug in nonhemophilic subjects. “Thus, it’s important in clinical trials that this drug not be given to control subjects because, for them, it may cause unwanted platelet activation and, thus, clot formation,” said Naik.
The study, “Fucoidan Is a Novel Platelet Agonist for the C-type Lectin-like Receptor 2 (CLEC-2),” was published in The Journal of Biological Chemistry on March 15, 2013.
Source: University of Delaware (UDaily), April 2, 2013