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Antidote could reverse effects of some drugs

Some medicines may soon have an undo button.

Researchers at Duke Translational Research Institute and Duke Clinical Research Institute have joined to develop a universal antidote for aptamer drugs—medications made of DNA or RNA that bind to the surface of harmful proteins and inhibit their function. Although the universal antidote—which is able to reverse effects of eight aptamer compounds—has not yet been tested in humans, an antidote tailored to counteract a blood-thinning drug has been successful in 200 clinical trials with human patients.

Bruce Sullenger, director of DTRI, was prompted to develop this antidote by cardiologists who wanted more control over the activity of blood-thinners used in heart surgery, which, like most drugs, can have dangerous side effects.

“[Doctors] use the analogy that they feel like [it’s] when you send an e-mail that you hastily did... there’s no way to retrieve it, so you’re basically stuck,” Sullenger said. “[With the antidote you have] the ability to pull back that e-mail.”

For the millions of patients who require stints in their hearts each year, a blood thinning drug antidote may be a source of relief. Blood thinning drugs used in heart surgery cause excessive bleeding in 15 percent of patients, a problem usually corrected with blood transfusions that can decrease surgical success if administered while the patient is bleeding.

The antidote Sullenger’s team created counteracts an aptamer blood thinner still being tested in clinical trials, Sullenger said. It acts like a sponge to the drug, sopping it up and stopping its activity.

Heart surgery is not the only situation where a universal antidote could help.

“The universal antidote represents the next frontier of regulatable therapeutics,” said Dr. Richard Becker, professor of medicine and a DCRI scientist.

Sullenger said the antidote would make drugs safer, especially in situations where medications need to be rapidly controlled.

“We predict that this antidote technology will greatly expand the number of diseases that can be treated with safer medicines,” Sullenger wrote in an e-mail.

With a growing number of people taking multiple medications, the need to limit side effects has become greater, he added. A universal antidote could increase the safety of multiple drugs at once.

The side effects of aptamer drugs are no different than those of other drugs, Sullenger said

“The problem is that we haven’t been able to control the side effects of any real class of drugs easily, so what we’re excited about... is that here’s a class of drugs that is amenable to control,” Sullenger said.

Dr. Robert Harrington, director of DCRI, said this research could result in new treatment approaches for patients.

Sullenger’s original idea was to create aptamer drugs and their antidotes in pairs, with a separate antidote for each drug. The blood thinner and its antidote were the first of these pairs. Funding new drugs is costly, however, prompting Sullenger to develop the universal antidote.

There is only one aptamer drug—which blocks new blood vessel growth—currently on the market, but many more are in clinical development. Sullenger said he hopes the universal antidote will be ready for human clinical trials in two years.


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