Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Designing drugs and their antidotes together improves patient care

06.10.2009
Imagine a surgical patient on a blood-thinning drug who starts bleeding more than expected, and an antidote that works immediately – because the blood thinner and antidote were designed to work together. Researchers at Duke University Medical Center have engineered a way to do this for an entire, versatile class of drugs called aptamers and published their findings in Nature Medicine.

"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," said Bruce Sullenger, Ph.D., senior author and Vice Chair for Research and Joseph W. and Dorothy W. Beard Professor of Surgery. Yet bleeding is a common side effect during and after treatments that require anticoagulation therapy such as surgery or angioplasty.

These new antidotes may give doctors a way to quickly and precisely put the brakes on an anticoagulant if bleeding becomes a problem or neutralize other adverse events or toxicities.

Duke researchers have just completed a series of successful clinical trials in patients taking a blood-thinner aptamer and an antidote engineered to reverse the effects of the aptamer.

"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," Sullenger said. Their approach amounts to a universal antidote to the entire aptamer family. "We predict that this advance will significantly expand the number of diseases that can be more safely treated using antidote-controllable therapeutic agents," he said.

The new approach, called RNA-based aptamer technology, "provides the opportunity to make safer drugs," said Sullenger, who also directs the Duke Translational Research Institute. "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 bind to a specific target molecule. If a patient takes an aptamer drug, the drug is the only free oligonucleotide in the body.

The researchers studied eight aptamer drugs and showed that the antidotes they introduced could reverse the activity of any of the drugs, regardless of the sequence, shape or target of the drug.

One advantage of aptamer drugs, as opposed to antibody-based drugs, is that nucleic acids aren't typically recognized by the human immune system as foreign agents. Aptamers do not generally trigger an immune response, Sullenger said.

"This technology could be applied to any oligonucleotide-based therapeutic that is free in a patient's circulation," said lead author Sabah Oney, Ph.D., formerly with the Sullenger laboratory and now a senior scientist at b3bio, a biotechnology company Sullenger helped co-found in the Research Triangle Park.

"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," Oney said. "This could be rapidly translated into the clinic, and lead to a whole new class of safer therapeutic agents."

To date, one aptamer has been approved by the U.S. Food and Drug Administration, a drug for macular degeneration, a cause of blindness. Several others are being tested and developed for use in cardiovascular, hematology and cancer patients.

"This research potentially represents the next frontier of controlled therapeutics using nucleic acids as highly selective antithrombotics and neutralizing polymers," said Richard C. Becker, M.D., Professor of Medicine in the Duke Divisions of Cardiology and Hematology and a scientist in the Duke Clinical Research Institute (DCRI) who has worked on clinical trials with the aptamer antidotes. "The translational platform for antithrombotic therapy pioneered by the Sullenger laboratory in collaboration with the DCRI underscores the unlimited potential of clinicians and scientists collaborating with purpose and commitment to advance patient care."

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

Other authors on the paper include Ruby T. S. Lam of the Duke Department of Biomedical Engineering, Kristin M. Bompiani and Charlene M. Blake of the Duke University Program in Genetics and Genomics and the Duke Department of Surgery, George Quick of the Duke Translational Research Institute, Jeremy Heidel and Joanna Yi-Ching Liu of Calando Pharmaceuticals, and Brendan C. Mack and Mark E. Davis of the Department of Chemical Engineering at the California Institute of Technology.

This work was supported by a grant from the National Institutes of Health, a predoctoral fellowship from the American Heart Association, and a grant from the National Cancer Institute.

Mary Jane Gore | EurekAlert!
Further information:
http://www.duke.edu

More articles from Health and Medicine:

nachricht Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>