When too many blood platelets stick together in the bloodstream, they form dangerous clots that can clog blood vessels and cause a heart attack. If a clot doesn't get dissolved or rapidly removed, it can cause permanent damage or even death.
But new research by Rockefeller University scientists suggests that it should be possible to create a clot-busting pill that targets a receptor on the blood cells' surface, something that high-risk patients could take at the first sign of chest pain.
Platelets are the blood's search and rescue team, rushing to the site of an injury and sticking together to help prevent excessive bleeding. Unfortunately, when they perform the same activity in a narrowed artery with atherosclerosis, they can produce a dangerous clot. A few powerful medications exist that can completely prevent them from sticking together, but doctors must administer the drugs intravenously. With a pill, patients could keep it in their medicine cabinets, saving precious time and preventing excess damage.
The key to such a pill, the Rockefeller scientists say, is a receptor called áIIbâ3 on the platelets' surface that is intimately involved in the aggregation process. Interfering with áIIbâ3 can prevent an unwanted clot or 'thrombus,' and the three áIIbâ3 inhibitors currently on the market can do just that. But they also have side effects and risks. Barry Coller, David Rockefeller Professor and head of the Allen and Frances Adler Laboratory of Blood and Vascular Biology, and laboratory manager Robert Blue have found a new molecule, called RUC-1, that not only appears to sidestep these problems but, unlike existing drugs, could be taken orally.
The áIIbâ3 receptor is made up of two halves: the áIIb subunit and the â3 subunit. Previous attempts to create áIIbâ3 inhibitors that could be taken orally led to drugs that bind to both halves; this blocks other platelets from attaching, but also changes the configuration of the receptor to its 'on' position. Once the drug wears off, the inhibitor may leave the receptor in the on position, making the platelet primed and ready for other passing platelets to bind. "As a result, once the inhibitor is gone and the receptors are still in the active conformation, you get a paradoxical increase in thrombus formation," Blue says.