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
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences