In a new study, researchers reveal how a drug based on the structure of trowaglerix - a protein derived from the venom of the Tropidolaemus wagleri snake - effectively reduced the formation of blood clots in mice, without the side effect of excessive bleeding.
Study co-author Jane Tseng, Ph.D., of the Graduate Institute of Biomedical Electronics and Bioinformatics and Drug Research Center at National Taiwan University in Taipei, and colleagues believe that the drug could provide a safer alternative to current antiplatelet medications.
The findings were recently published in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.
Antiplatelets are a class of drugs commonly used for the prevention and treatment of stroke, heart attack, and heart disease. They work by preventing a type of blood cell called platelets from clumping together, which therefore reduces the formation of blood clots.
While current antiplatelet medications - such as aspirin, clopidogrel, and glycoprotein IIb/IIIa antagonists - can be effective for reducing blood clot formation, one major side effect is excessive bleeding after injury.
Dr. Tseng and colleagues believe that trowaglerix could pave the way for a new antiplatelet drug that is just as effective, but which does not cause excessive bleeding.
Trowaglerix-based drug did not lead to excessive bleeding in mice
In previous research, Dr. Tseng and team found that trowaglerix interacted with glycoprotein VI (GPVI) - a protein that resides on the surface of platelets - to form blood clots.
Studies have indicated that platelets lacking in GPVI do not have the ability to form blood clots, and this reduces heavy bleeding in humans. As such, researchers speculate that inhibiting GPVI not only has the potential to prevent blood clotting, but they also believe that it could prevent excessive bleeding.
By looking at the structure of trowaglerix, Dr. Tseng and colleagues were able to create a drug that blocks GPVI activity.
On testing the newly developed drug on platelets, the researchers found that it stopped them from clumping.
The team also tested the drug in mice. Compared with mice that were not treated with the drug, the treated mice experienced slower blood clot formation. What is more, the treated mice did not bleed for any longer than the untreated rodents.
Overall, the researchers believe that their findings indicate that the trowaglerix-based drug may offer a safer, effective strategy to prevent blood clots. However, the team notes that further studies are needed to determine the drug's safety and efficacy in humans.
"In general, this type of molecule design does not last long in the body, so techniques like formulation or delivery system are likely needed to extend the exposure time in the human body," says Dr. Tseng.
"The design must also be optimized to ensure that the molecule only interacts with GPVI and not other proteins which can cause unintended reactions."
The researchers say that they are already looking at ways to improve the design of their molecule.