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Weizmann institute scientists solve the 3-D structure of the enzyme involved in Gaucher disease

Rehovot, Israel -- June 2, 2003 --An interdisciplinary team of Weizmann Institute scientists has solved the three-dimensional structure of an enzyme called glucocerebrosidase. Mutations occurring in this enzyme cause Gaucher disease, a genetic illness that mainly affects Ashkenazi Jews. The Institute study, published recently in EMBO Reports, may lead to the design of effective new therapies for treating the disease.

Gaucher disease was first described in 1882 by the French physician Philippe Gaucher. It is characterized by swelling and enlargement of the spleen and liver and disruption in the function of these organs, and in rare cases it also affects the brain. In the 1920s, the disease was found to be caused by the excessive accumulation of a fatty substance, or lipid, called glucosylceramide. In the 1960s, researchers discovered that the accumulation occurs due to a defect in the glucocerebrosidase enzyme, whose function is to break down this lipid and regulate its amount. In the 1980s, the gene responsible for manufacturing the enzyme was isolated; scientists found that mutations in this gene disrupt the function of the enzyme, leading to the development of Gaucher disease.

By the early 1990s, the U.S. company Genzyme started producing the enzyme first from placenta, then by genetic engineering. Today thousands of Gaucher patients are treated by injections of the enzyme, an approach called enzyme replacement therapy, or ERT. The annual cost of the therapy per patient is approximately $100,000 to $300,000. Obviously, more affordable alternatives, such as the ones that may emerge from the Weizmann Institute study, are urgently needed.

The Institute team included Prof. Tony Futerman of the Biological Chemistry Department, Prof. Joel Sussman of the Structural Biology Department and Prof. Israel Silman of the Neurobiology Department, as well as Dr. Michal Harel, Lilly Toker and graduate student Hay Dvir.

The first step in solving th
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Contact: Alex Smith
Alex_smith@margeotes.com
212-460-0563
American Committee for the Weizmann Institute of Science
1-Jun-2003


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