A new possibility is being developed in Australia for anticoagulation therapy drugs...
Excerpts from TheHeart.org:
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The drug has several years to go, but it has started on the road for government acceptance.
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Excerpts from TheHeart.org:
From: http://www.theheart.org/viewArticle.do?primaryKey=439539&nl_id=tho22apr05Heart Wire Apr 21, 2005 Michael O'Riordan
New target for antithrombotic therapy discovered
Victoria, Australia - Australian researchers have identified a potential new target for antithrombotic therapy, leading to the development of a new class of drugs that reduce thrombus formation and prevent the development of occlusive thrombi without the associated risk of bleeding.[1]
"...the most striking observation about these drugs...is that we have a drug that works extremely rapidly at stopping occlusions in the blood vessels," lead investigator Dr Shaun Jackson (Monash University, Victoria, Australia) told heartwire. "Yet despite combining it with other drugs, including other antithrombotic agents, it really has very little effect on the normal hemostatic process. It's quite remarkable. We've not seen a drug like this before."
The target for therapy is an enzyme known as phosphoinositide (PI) 3-kinase p110...Previous studies have implicated these enzymes in the formation of platelet bonds under high stress, but...Jackson and colleagues were able to show that this isoform plays a critical role in platelet bond stability.
"As the blood vessel narrows because of atherosclerosis, and there is a clot building up,...the blood flow where the occlusion is becomes quite rapid and the shear stress is high," said Jackson. "This can further promote platelet activation...this enzyme is critical for that process. Our experiments showed that [PI 3-kinase p110] plays an important role in sustaining the activation of integrin necessary for the formation of a stable clot. If you inhibit the enzyme, the integrin cannot sustain those platelet bonds, and the bonds become unstable."
After identifying PI 3-kinase p110 as having a role in the development of a thrombus under high shear stress, the investigators were able to develop an isoform-selective PI 3-kinase p110 inhibitor. The premise was that blocking the enzyme would prevent the formation of stable platelet bonds, leading to defective thrombus formation.
The researchers investigated the antithrombotic potential of the platelet inhibitor, known as TGX-221, in a variety of animal models...TGX-221...abolished occlusive thrombus formation in 100% of rats and rabbits. The effect was selective and rapid, occurring within five minutes. In a separate carotid-artery injury model in rats, TGX-221 prevented the development of occlusive thrombi and was more effective than aspirin at preserving carotid blood flow after the injury.
"We...," said Jackson, "...have consistently shown...that when we infuse these inhibitors, the clots aren't able to occlude the vessel...Compared with drugs such as aspirin, particularly in the high shear models, we see that these drugs are more effective than aspirin at preserving blood flow."
The administration of TGX-221 with an anticoagulant such as heparin (100 U/kg intravenous) also had no significant effect on bleeding time, a finding that left the researchers surprised.
"I don't think we've ever seen a drug that doesn't prolong bleeding time when you combine it with an anticoagulant," Jackson told heartwire. He added that one of the PI 3-kinase p110 inhibitors has gone through a formal preclinical toxicity program, with the agent looking "extremely promising."
Commercial rights to the PI 3-kinase p110beta inhibitor are held by Cerylid Biosciences, and several researchers participating in the study were full-time employees of Kinacia, a wholly owned subsidiary of Cerylid Biosciences...The study was partially funded by Kinacia and the National Health and Medical Research Council and the National Heart Foundation of Australia.
You will need to register with the site, if you wish to read the rest of the article.
The drug has several years to go, but it has started on the road for government acceptance.
Best wishes,
