New anticoagulant drug-plus-antidote system passes initial safety trials

The first-ever anticoagulant drug-plus-antidote system has passed initial safety trials at Duke University in Durham, N.C. The new platform combines a short nucleic acid chain that quickly blocks clotting with an antidote that removes the clotting blockage in minutes.

"We intend to develop this molecule for coronary artery disease in a variety of settings," said Richard Becker, MD, professor of medicine at the Duke University Medical Center. "This platform can be used for many disease states."

The drug-antidote combination targets Factor IXa, part of the signaling cascade that activates thrombin and coagulation. A protein-binding, single-strand nucleic acid called an aptamer is engineered to lock into a surface receptor and deactivate Factor IXa to halt coagulation. The new molecule has been dubbed REG1 after Regado, a biotechnology company founded by Duke researchers to commercialize their discovery.

The antidote, a second aptamer, binds to REG1, changing its shape slightly, which causes it to release bound Factor IXa molecules and restart coagulation. Both the drug and antidote have acted in 1 to 5 minutes in phase 1 trials.

Dr. Becker said REG1 could be used in angioplasty, dialysis, and heart-lung bypass, among other cardiac applications. One of the earliest uses could be as a substitute for heparin, which is relatively difficult to use, nonspecific in action, and subject to adverse events.

The same drug-antidote platform could be used to treat a variety of conditions, including infectious disease, different forms of arthritis, and cancer, according to researchers.

"This technology can target just about any small molecule associated with any disease," Dr. Becker said. "If a disease or an organism has an identifiable signature, any feature that makes it distinct and identifiable, an aptamer should be able to lock onto it."