Duke Testing DNA-Based Switch to Control Blood Clotting

DURHAM, N.C. — Physicians at Duke University have created a system to control the body's blood-thinning and clotting ability that might one day become the standard of care around the world.

Blood-thinning drugs like Heparin and Coumadin prevent blood clots and help head off heart attacks, strokes and deep-vein thrombosis. But they also increase the risk of uncontrolled bleeding, especially during surgery.

Duke researchers believe they have solved the bleeding problem with a DNA-based system called REG1.

The system uses aptamers -- short strings of single-stranded nucleic acids, either DNA or RNA -- that bind to specific protein or small-molecule targets. Doctors can use the binding pair to control the degree of blood thinning that takes place and to reactivate clotting within five minutes.

"The basis for developing this particular drug antidote pair (was) so that we could thin the blood, thin it rapidly, but we could reverse the effects with a true antidote," said Dr. Richard Becker, the director of Duke's Thromosis Center. "The blood would go back to its normal clotting potential. Surgery could take place. Then, if need be, if there was an indication, we could re-thin the blood."

Becker said the antidote is inert and quickly leaves the body after it turns off the blood-thinning switch.

Regado Biosciences Inc., a Duke spin-off, developed the anticoagulant-antidote pair based on technology licensed from Duke. The company also is sponsoring the clinical trials.

In the Phase 1 trial, 85 young, healthy people took part. Becker said there were no problems with bleeding and the antidote worked well.

Now, physicians are trying the system on older patients with stable heart disease who are already on blood-thinning drugs like aspirin. Researchers also are trying to identify potential side effects.