Troy, N.Y. In early 2008, there was a frightening failure in drug safety processes. In just a few weeks, more than 100 Americans had died after being administered contaminated doses of the common blood thinner heparin. The contaminant, present in heparin manufactured in China and discovered with the help of scientists from Rensselaer Polytechnic Institute, was so structurally similar to pure heparin that is was undetectable to all but the most sophisticated detection techniques. As a result, many people became seriously ill or died around the world and the several hundred thousand patients that receive the drug every day in the U.S. were put at risk.
The health crisis pointed to very large problems with the safety processes surrounding heparin, which is one of the most commonly administered drugs in American hospitals today. Most notably, it called worldwide attention to the risks posed by a product made nearly entirely of material from the guts of foreign livestock in less stringently regulated overseas factories. With a $4.6 million grant from the National Institutes of Health (under the Bioengineering Research Partnership program), research led by Rensselaer Polytechnic Institute will make its important final steps toward the development of a safer, synthetic alternative to current heparin. The researchers believe that kilogram quantities of the new drug could be developed in under five years.
"Our goal is to create a bioengineered heparin that is chemically and biologically equivalent to pharmaceutical heparin currently prepared from pig intestines," said Jonathan Dordick , one of the lead researchers for the study, who is the Howard P. Isermann Professor of Chemical and Biological Engineering and Director of the Center for Biotechnology and Interdisciplinary Studies (CBIS). "Our process will improve the safety and uniformity of heparin and prevent future contamination or adulteration of the important drug."
Dordick will be joined by co-principal investigator and project director for the partnership grant, Robert Linhardt, who is the Ann and John H. Broadbent Jr. '59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer. Linhardt, who was recently named one of the Scientific American 10, is among the world's foremost experts on heparin. His lab led the effort to find the contamination in 2008. And while Linhardt continues to develop more sophisticated detection systems to ensure a safer stream of drugs to the marketplace, he is also helping lead the race for a safer, man-made alternative to the traditional biologic heparin.
Linhardt helped discover the "recipe" for synthetic heparin three years ago with Jian Liu of the University of North Carolina. In August 2008, Linhardt announced that his team had constructed a milligram quantity of the purer, safer alternative creating the first fully synthetic heparin, and the largest amount ever created in the laboratory. Now he joins Dordick and fellow principal investigators Research Associate Professor of Chemical and Biological Engineering Fuming Zhang; Associate Professor Jian Liu from the University of North Carolina; and Professor Shaker Mousa from Albany College of Pharmacy, to scale up their capacity to manufacture the drug from a milligram to a kilogram a million-fold increase. A kilogram quantity of the drug would provide a strong foundation for the production of the millions of doses of the drug that would be required each year, according to the researchers.
"We believe a replacement for the currently available heparin is truly within our grasp," Linhardt said. "Some of the most important priorities of the research from here will be to create a simple and cost-effective process that can be easily replicated to produce a bioengineered, non-animal heparin at scales and cost sufficient to satisfy the therapeutic needs in the U.S."
The NIH grant totals nearly $4.7 million and will fund five years of study. The main goals of the project will be to optimize the production of bioengineered heparin, confirm its chemical equivalence to the current heparin, and to scale-up production of kilogram quantities.
|Contact: Gabrielle DeMarco|
Rensselaer Polytechnic Institute