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Novel drug-antidote strategy provides greater control of drug action

of the anticoagulant effects of the drug within 10 minutes, and continued to neutralize the anticoagulant activity more than an hour later," Sullenger said.

In studies conducted by colleagues from the University of Michigan, the aptamer drug-antidote pair was successful in mouse models. The drug effectively prevented arterial thrombosis in murine thrombosis models, and the additional safety of the drug conferred by the antidote was demonstrated in murine surgical challenge models. Mice were treated with high doses of the anticoagulant and the ends of their tails were clipped off. Mice who were not given the antidote experienced significant bleeding in response to this surgical challenge, whereas mice given the antidote after the tail clipping experienced no increased blood loss.

"Our studies demonstrate that the aptamer anticoagulant is effective in clinically predictive animal models of cardiovascular disease and that its antidote prevents the potential side effects of this new drug," Sullenger said.

The researchers said that while there will be many potential uses of this new approach to drug development, the first clinical application will likely be in the area of open heart surgery. In order to place a heart on the heart-lung machine, the blood must be thinned to prevent clotting in the machine's tubing during surgery. However, once the surgery is complete, the blood must be returned to its proper state.

"For decades, surgeons have used heparin to thin the blood of these patients, and the only agent available to block the effect of heparin is protamine," Rusconi said. "However, heparin and protamine are imperfect drugs, with many unwanted side effects. This new aptamer-based drug and its antidote have the potential to give surgeons much more control over anti-coagulation."

Cardiologists routinely use blood-thinning or anti-coagulant agents as an urgent treatment for
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Contact: Richard Merritt
Merri006@mc.duke.edu
919-684-4148
Duke University Medical Center
17-Oct-2004


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