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Researchers Create Safer Alternative to Heparin

Sun, 2008-08-17 14:30 -- Anonymous

August 17, 2008

Larger amounts of fully synthetic heparin could be ready for use in patients in five years

Robert Linhardt has spent years stitching together minuscule carbohydrates to build a more pure and safer alternative to the commonly used and controversial blood thinner heparin. At the national conference of the American Chemical Society on August 17, 2008, Linhardt announced that his research team may have accomplished this task by building the first fully synthetic heparin. Their creation is the largest dose of heparin ever created in the lab.

Heparin is used around the globe and is among the most widely used drugs in American hospitals. The main source of this heparin is the intestines of foreign livestock and the risk of contamination from such sources is high, according to Linhardt. And as Linhardt and others around the globe worked toward an alternative, drug manufacturers worked to avoid contamination, but the risks proved too high, Linhardt said. In the spring of 2008, the search for a safer alternative to the common drug had reached a frantic pace after more than 80 people around the world died and hundreds became ill after they were administered what was believed to be contaminated batches of heparin.

Linhardt, who is the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer Polytechnic Institute, was on the international team that identified the suspected contaminant in the Chinese heparin, a structurally similar carbohydrate called oversulfated chondroitin sulfate. 

“When we found the contamination, it was another sign that the way we currently manufacture heparin is simply unsafe,” he said. “Unlike the current heparin that is harvested from possibly disease carrying animals in often very poor conditions, our fully synthetic heparin will be created in a pharmaceutical manufacturing environment from fermentation to packaging. This will give drug manufacturers extreme control over the safety and purity of the product.”

Linhardt, together with Jian Liu of the University of North Carolina, discovered the synthetic “recipe” for heparin in 2006. Since that time he has worked to piece together the various molecules and grow a complex carbohydrate that is naturally created in the body in the lab. The carbohydrate backbone for the new heparin comes from the bacteria E. coli. The use of the common and easily grown bacteria makes this version of heparin much easier and faster to produce, according to Linhardt. The team used a process called chemoenzymatic synthesis that used specialized synthetic chemicals and natural enzymes expressed in E. coli to replicate the normal biosynthesis of natural heparin within the cell.

The dose that Linhardt and his team were able to produce with this method was a million times higher than any other alternative created to date. He will now continue to work with his partners to take the milligram dose that they have developed and expand it to kilograms. “Ultimately, drug companies are going to need to produce tons of this drug to keep up with global demand,” he said. “Such levels of productions are further down the road. We think that in five years, it is very possible that this drug could reach human clinical trials.” 

The milligram-scale synthesis of heparin will be published in the Journal of the American Chemical Society. To complete the research, Linhardt was joined by Zhenqung Zhang, Scott McCallum, and Jin Xie at Rensselaer; Lidia Nieto and Jesus Jimenez-Barbero at Centro de Investigaciones Biologicas; Francisco Corzana at Universidad de La Rioja UA-CSIC; and Miao Chen and Jian Liu at the University of North Carolina, Chapel Hill. He is currently working with Jonathan Dordick at Rensselaer and Jian Liu from Chapel Hill and Shaker Mousa from Albany College of Pharmacy to create and evaluate the larger batches of the drug.

Contact: Jason Gorss
Phone: (518) 276-6098
E-mail: gorssj@rpi.edu