The team, led by Professor Ram Sasisekharan of MIT, identified the chemical structure of the contaminant, known as oversulfated chondroitin sulfate (OSCS). The researchers present their findings and offer new approaches to detecting the contaminant in a report appearing today in the online edition of Nature Biotechnology.
Another team led by Sasisekharan has shown exactly how OSCS can kill- specifically by setting off an allergy-like reaction. The biological effects of the contaminant are outlined in a report also being published online today in the New England Journal of Medicine.
“Sophisticated analytical techniques enabled complete characterization of the contaminant present in heparin. Further, this study also provides the scientific groundwork for critical improvements in screening practices that can now be applied to monitor heparin, thus ensuring patient safety,” said Sasisekharan, senior author of the papers and the Underwood Prescott Professor of Biological Engineering and Health Sciences and Technology at MIT.
Heparin, a blood thinner often used during kidney dialysis or heart surgery, is normally produced from pig intestines. FDA officials say the contaminated heparin came from factories in China that manufacture the drug for Baxter International.
Baxter recalled its heparin in February after dozens of deaths were reported, dating back to November. The tainted heparin has been blamed for 81 U.S. deaths so far, and earlier this week, the FDA announced that contaminated batches were also found in 10 other countries.
The New England Journal of Medicine study offers the first potential link between the contaminant and the reported deaths. The researchers found that the contaminated heparin activates two inflammatory pathways, causing severe allergic reactions and low blood pressure.
“These results provide a potential link between the presence of chemical contaminant in heparin and the clinical symptoms observed in affected patients. Our findings also suggest that a simple bioassay could help protect the global supply chain of heparin, by screening heparin lots for the presence of polysulfated contaminants that may have unintended pharmacological consequences,” said Sasisekharan.
Heparin consists of a long, complex chain of repeating sugar molecules. The contaminant, which is derived from animal cartilage, has a structure very similar to that of heparin and thus cannot be identified with the tests normally used to inspect batches of heparin.
It is unclear whether the contaminant got into the heparin during the manufacturing process, or how and where contamination could have occurred during the process. More investigations are needed to address this issue.
Traditional heparin safety screens test only for contaminants such as protein, lipids or DNA, and thus would not detect the presence of sugar chains that do not belong. Sasisekharan's laboratory has played a key role in developing new technologies for analyzing complex sugars. Using the new technology, the research team was able to detect the presence of the faulty sugars.
“In addition to being vital for public health, identifying the recent impurity in heparin was a chemical triumph,” said Jeremy M. Berg, director of the National Institute of General Medical Science, which supported the work. “The research team accomplished this difficult task by using a unique combination of scientific techniques that might in the future be used to detect other impurities in pharmaceutical materials.”
More than 100 patients have experienced adverse reactions after receiving the tainted heparin. Symptoms include extremely low blood pressure, swelling of the skin and mucus membranes, shortness of breath, and abdominal pain.The researchers found that the contaminant activates two inflammatory
Sasisekharan emphasized the remarkable willingness of dozens of scientists across the globe to work together to rapidly resolve what might otherwise have left people with serious uncertainties about drug safety.
“The generosity and willingness of people to do whatever they could to help solve this problem was unlike anything I'd experienced before. It is extremely satisfying to see how teamwork has resulted in the application of rigorous, peer-reviewed science that helps to keep our medicines safe,” he said.
Sasisekharan expressed his hope that such effective teamwork will extend to other dimensions of public health, in which rigorous team- based science leads not only toward safer drugs, but also toward safer foods and a safer environment.
Researchers from the FDA, Momenta Pharmaceuticals of Cambridge, Mass., Rensselaer Polytechnic Institute and the Istituto di Recherche Chimiche e Biochimiche of Milan, Italy, also contributed to the Nature Biotechnology paper.
Researchers from the FDA, Momenta Pharmaceuticals, Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech, and Brigham and Women's Hospital contributed to the New England Journal of Medicine paper.
Anne Trafton | MIT News Office
Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University
ASU scientists develop new, rapid pipeline for antimicrobials
14.12.2017 | Arizona State University
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
14.12.2017 | Health and Medicine
14.12.2017 | Physics and Astronomy
14.12.2017 | Life Sciences