Duke UniversityIf a surgical patient is on a blood-thinning drug and he begins to bleed more than anticipated, and if an antidote works instantly, then that could mean that the blood thinner drug and antidote were apparently designed to function together. Bearing the topic in mind, it is claimed by the researchers at Duke University that they have apparently engineered a method to do this for a complete, versatile class of drugs known as aptamers.

These new antidotes may give doctors a means to swiftly and accurately put the brakes on an anticoagulant if bleeding may become a problem or counterbalance other unfavorable proceedings or toxicities.

Duke researchers have apparently just finished a chain of successful clinical trials in patients taking a blood-thinner aptamer and an antidote which may be engineered to undo the effects of the aptamer.

Bruce Sullenger, PhD, senior author and Vice Chair for Research and Joseph W. and Dorothy W. Beard Professor of Surgery, commented, “With any anticoagulant, you are trying to reduce your chances of having clotting because it can lead to a heart attack or stroke during treatment.”

Nevertheless, bleeding may be a general side effect during and after treatments that could need anticoagulation therapy like surgery or angioplasty.

Sullenger added, “We have shown that this type of antidote can reverse the action of any of the aptamer drugs, and there are many aptamers in development. We predict that this advance will significantly expand the number of diseases that can be more safely treated using antidote-controllable therapeutic agents.”

The new approach is known as the RNA-based aptamer technology and it may supply the occasion to create safer drugs.

Sullenger, who also directs the Duke Translational Research Institute, mentioned, “And now that we can engineer a universal antidote for aptamers, we can in principle for the first time afford to provide additional control over drugs for patients and their physicians.”

Aptamers are oligonucelotides, short stretches of nucleic acid that may combine to a particular target molecule. If a patient takes an aptamer drug, the drug is said to be the only free oligonucleotide in the body.

The researchers examined about eight aptamer drugs and demonstrated that the antidotes they introduced could undo the activity of any of the drugs, in spite of of the sequence, form or objective of the drug.

Sullenger mentioned that one benefit of aptamer drugs, as compared to antibody-based drugs, is that nucleic acids may not be usually identified by the human immune system as foreign agents. Aptamers may not generally activate an immune response.

Lead author Sabah Oney, PhD, formerly with the Sullenger laboratory and now a senior scientist at b3bio, a biotechnology company Sullenger helped co-found in the Research Triangle Park, commented, “This technology could be applied to any oligonucleotide-based therapeutic that is free in a patient’s circulation. With the ever-increasing number of such drugs in clinical trials, we believe that this discovery can have very broad applications and improve the safety profile of these therapeutics. This could be rapidly translated into the clinic, and lead to a whole new class of safer therapeutic agents.”

Kam Leong, a James B. Duke professor of biomedical engineering and co-author of the research, remarked, “Future optimization should further improve the potency of sequestering the aptamers from circulation, which will then spur the development of many new aptamer drugs.”

One aptamer drug has apparently been accepted by the U.S. Food and Drug Administration. This is a drug for macular degeneration, which could be a reason for blindness. Various others are being tested and developed for use for cardiovascular, hematology and cancer patients.

This research was published in Nature Medicine.