Yesterday I happened to see a tweet from the Ohio State University Medical Center's twitter account that linked to a press release discussing a new plasminogen activator that is currently undergoing clinical trials. The drug, desmoteplase, is modeled after a protein found in vampire bat saliva that prevents clots and platelet aggregation, which keeps the blood flowing while the bat is feeding. Plasminogen activators like desmoteplase are used to break down blood clots that are blocking blood flow to vital organs such as the heart, lungs, or brain.
|Anatomy of a heart attack.|
Image credit: Flickr user gandhiji40
After the vessel heals and the clot is no longer needed, a chemical called plasminogen is activated and becomes plasmin. Plasmin then breaks down the clot by solubilizing fibrin. This is a safe way to get rid of the clot so that it doesn't come off in one piece and then lodge itself into a small vessel where it can cut off circulation to parts of the body. However, sometimes clots are not broken down properly and can cut off blood flow to the brain (stroke) or heart (heart attack). When this happens, we need to manually turn plasminogen into plasmin using plasminogen activators, so that plasmin can break down the clot and restore blood flow.
|Vampire bat, Desmodus rotundus.|
Image credit: Flickr user Robertsphotos1
Desmoteplase, which is derived from the plasminogen activators in vampire bat saliva originally described by Hawkey, seems to have some advantages over currently used plasminogen activators (which are often based on chemicals in humans). Current drugs are only approved for use up to 3 hours after symptom onset, and Dr. Michel Torbey at OSU MC is hopeful that desmoteplase will demonstrate efficacy up to 9 hours after symptom onset, which could drastically reduce the number of deaths. From the press release:
"Prompt medical care within three hours is very important for recovery from a stroke, but attempts to find drugs that extend the treatment window have not been successful," added Torbey. "If the study findings back up our hopes and expectations, desmoteplase could be a real game changer in our ability to help patients."
In addition to expanding the treatment window, desmoteplase is more potent and specific than current drugs. One current plasminogen activator is even linked to neurotoxicity in some patients, so there is high demand for newer and better drugs to treat problematic clots. If approved, this drug could reduce the risk of death in stroke patients who live in remote areas and may not be able to make it to the emergency room within the three hour window.
HAWKEY, C. (1966). Plasminogen Activator in Saliva of the Vampire Bat Desmodus rotundus Nature, 211 (5047), 434-435 DOI: 10.1038/211434c0
Hawkey, C. (1967). Inhibitor of Platelet Aggregation Present in Saliva of the Vampire Bat Desmodus rotundus British Journal of Haematology, 13 (6), 1014-1020 DOI: 10.1111/j.1365-2141.1967.tb08870.x
Schleuning, W. (2001). Vampire Bat Plasminogen Activator DSPA-Alpha-1 (Desmoteplase): A Thrombolytic Drug Optimized by Natural Selection Pathophysiology of Haemostasis and Thrombosis, 31 (3-6), 118-122 DOI: 10.1159/000048054