NEW YORK (Reuters Health) - Scientists have developed and successfully animal tested an experimental anticoagulant aptamer that provides potent anticoagulation as well as a matched antidote that can quickly reverse the activity and thus the side effects (e.g. bleeding) of this blood thinner.
The anticoagulant-antidote pair may have “broad utility” in the medical treatment of patients with acute coronary syndrome as well as during coronary revascularization procedures, they suggest in an advance online issue of Nature Biotechnology released Sunday.
The anticoagulant aptamer Ch-9.3t specifically targets human coagulation factor IXa, which plays key roles in both the initiation and propagation phases of coagulation. Ch-9.3t induces systemic anticoagulation in pigs and inhibits thrombosis in murine models of cardiovascular disease, the scientists report.
Bolus injection of the 5-2C oligonucleotide antidote into anticoagulated animals rapidly and durably reverses greater than 95% of the anticoagulant effects of the aptamer and functionally restores hemostasis.
Moreover, the antidote completely prevented hemorrhage in the clipped tails of mice anticoagulated with Ch-9.3t, a finding that demonstrates the efficacy of the antidote in a surgical trauma model.
“Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients,” Dr. Bruce A. Sullenger from Duke University Medical Center in Durham, North Carolina and colleagues note in the article.
“These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.”
The team’s current findings build on work published in 2002, in which they describe a strategy for discovering antidote-controlled drugs and a first-version anticoagulant-antidote pair. (see Reuters Health report September 5, 2002).
“The drug-antidote pair technology we describe will allow for the development of antidote controlled drugs for a variety of indications where physicians want additional control of the drugs they use because of concern over patient safety,” Dr. Sullenger told Reuters Health.
Source: Nat Biotechnol 2004. [ Google search on this article ]
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