Indian MIT professor breaks new ground on sugars
Thursday, 16 January 2003, 20:30 IST
Printer Print Email Email
NEW YORK: The Massachusetts Institute of Technology (MIT) says its young Indian American professor Ram Sasisekharan's basic research on complex sugars has led to a cascade of potential medical applications. The findings of Sasisekharan's team could, for example, significantly improve outcomes for patients undergoing major operations such as heart bypass surgery and impact a multibillion-dollar drug industry, MIT emphasised. Sasisekharan is reportedly excited and a bit awed by the applications that are resulting from his work. "It's very often easier said than done to translate an idea to reality," he said. "To see it happen is really a humbling experience." In the latest issue of Proceedings of the National Academy of Sciences, a team led by Sasisekharan reports the creation of designer drugs for preventing the blood clots that can cause strokes and heart disease during surgery. The resulting drugs have major advantages over the conventional form they are based on, which has an annual market of $2-3 billion, said MIT in its release. Further, an additional drug based on Sasisekharan's work is presently in Phase III clinical trials for heart bypass patients. For over 60 years doctors have used the drug heparin -- the focus of the current research -- during surgeries. Although safe, heparin and its smaller cousin, low molecular weight heparin, have shortcomings based on the fact that there's been no quick and easy way to determine the exact amounts of the active ingredients of the drugs. "Simply put, low molecular weight heparins are essentially generated by chopping up heparin in a blender, which results in a mixture of large and small pieces with different amounts of active sites, or areas key to anticoagulation," said Sasisekharan, an associate professor in MIT's Biological Engineering Division. As a result, drug strengths vary from product to product and batch to batch. Sasisekharan's group has found the structure of those active ingredients and the tools to clip out only those sites from the bulk material. "This work started out as fundamental studies on complex sugars and has led to what may become an important new drug to treat conditions such as heart disease. It is an outstanding example of how basic research leads to cutting-edge technologies and medical advances," said Pamela Marino, a biochemist and programme director for glycobiology at the National Institute of General Medical Sciences, which partially supported the research. The research began with Sasisekharan's creation in 1992 of a ready supply of the molecular scissors, or heparinases, needed to "tailor" the heparins. He did so by cloning the heparinase gene, working with MIT professors Robert S. Langer and Charles L. Cooney. Since then Sasisekharan joined the MIT faculty, and with his graduate students and staff have used the heparinase scissors in several studies with wide-ranging implications, MIT said. First, the team developed a powerful technique for determining the order of building blocks in complex sugars like heparin leading to insights on heparin's active sites. Another study showed that cells' sugar jackets can be tailored to prevent cancer. In the latest paper, Sasisekharan's team reports the creation of two "designer" forms of low molecular weight heparin (LMWH), each with specially engineered properties, or activity profiles, more effective than currently used drugs, with a potential for additional applications. Scientists call this an important advance in the understanding of how heparin and related compounds work as anticoagulants but that the benefits of new designer heparin fragments now need testing in clinical trials. Authors of the paper are from MIT's Biological Engineering Division and Centre for Biomedical Engineering. In addition to Sasisekharan they are research affiliates Mallik Sundaram, Yiwei Qi, and Dongfang Liu (MIT Ph.D. 2001); research fellow Ganlin Zhao; visiting scientists Zachary Shriver (MIT Ph.D. 2001) and Ganesh Venkataraman (MIT Ph.D. 1993); and Langer, the Germeshausen Professor of Chemical and Biomedical Engineering who also holds an appointment in the Department of Chemical Engineering. In addition to the National Institute of General Medical Sciences, other supporters of the MIT research are the Burroughs Wellcome Foundation, the Arnold and Mabel Beckman Foundation and the CapCure Foundation. Sasisekharan, Langer and Venkataraman are also affiliated with Momenta Pharmaceuticals, where Venkataraman is vice president. Momenta Pharmaceuticals, in Cambridge, has licensed from MIT a variety of patents related to the work.
Source: IANS
siliconindia