Using blood thinners as a model, Medical Center researchers have found a potentially revolutionary method for designing safer drug treatments.
Their model would allow drugs to be created along with matching antidotes that could counteract an initial drug's effects when a patient experiences complications.
"This is the first time anyone's described a way to make a drug and its ready-made antidote," said Chris Rusconi, director of Duke's Research Program in Combinatorial Therapeutics and lead author of the study published in the Sept. 5 issue of Nature.
The research focuses on a class of drugs called aptamers, which are compounds of nucleic acid that bind to specific proteins and inhibit their activity. The antidote is composed of paired nucleic acids that bind to the aptamer, change its shape and thus neutralize it.
In the study, the scientists developed an aptamer that inhibits a protein necessary for blood clotting, as well as an antidote that was able to rapidly and permanently reverse the blood-thinning process.
"We chose to start with blood thinners because of the clinical need for safer treatments," said Bruce Sullenger, professor and vice chair of the surgery department and senior author of the study.
Blood thinners are administered to millions of patients every year. They are primarily used to prevent clotting during heart repair surgery and angioplasty and are also given to recent heart attack victims to ensure blood flow through the heart.
Although necessary for many heart treatments, common blood thinners frequently cause complications in patients, leading to hemorrhaging and sometimes death. Doctors frequently report the need for a reliable blood thinner antidote that would allow for precise control over the amount of bleeding in patients during surgical procedures, Sullenger said.
"The drug [we developed] allows for greater safety, so you can administer it without fear of bleeding," said Dougald Monroe, assistant professor of medicine at the University of North Carolina at Chapel Hill and a collaborator on the study.
Sullenger emphasized the value of the safer drugs to clinicians. "What we're trying to do is give physicians greater control over treatment... by giving an ability to call back a drug when a side effect develops," he said.
Rusconi added, "The feedback we're getting from physicians has been very enthusiastic."
Because aptamers are such a versatile class of drugs, used to treat nearly every kind of disease, the scientists have high hopes for expanding their technique.
"We have a vision of other potential applications, from oncology to anesthesiology, any place where a physician demands greater control," Sullenger said.
Rusconi agreed on the method's far-ranging potential. "It looks generalizable," he said. "You can do this time and time again."
As the study required scientific work in diverse areas, the researchers stressed the value of wide collaboration to their study. "Research of this type requires a team of scientists that spans a broad range of expertise," Rusconi said. "There are a lot of levels of science going on."
Sullenger and Rusconi particularly stressed the importance of communication between biological researchers and physicians who understand what is most needed for patient care and safety.
"The reason why this came about is the close interaction between biologists... and clinical people," Sullenger said. "I think Duke is one of the leaders from that perspective."
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