Deciphering Gaucher's Disease


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An interdisciplinary team of Weizmann Institute scientists has solved the 3-D structure of an enzyme involved in Gaucher's disease, a genetic illness that mainly affects Ashkenazi Jews. The study, published in EMBO Reports, may lead to the design of effective new therapies.
Gaucher's disease is characterized by swelling and enlargement of the spleen and liver and disruption in the function of these organs; in rare cases, it may also affect the brain. It is caused by the accumulation of a fatty substance, or lipid, called glucosylceramide. Accumulation occurs due to a defect in the enzyme charged with breaking down this lipid and regulating its amount.
Today thousands of Gaucher's patients are treated by injections of this enzyme, in an approach called enzyme replacement therapy, or ERT. The annual cost of the therapy is approximately $100,000 to $300,000 per patient. 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 solved enzyme structure may help in the design of a more effective enzyme that would improve today's ERT. It may also make possible the design of small molecules that will supplement the damaged enzyme in the patient's body, thereby restoring its normal functioning.
Prof. Futerman's research was supported by the Estate of Ernst and Anni Deutsch-Promotor Stiftung, Switzerland; the Paul Godfrey Foundation; the Buddy Taub Foundation; the Sir Siegmund Warburg's Weizmann Trust; and the Estate of Louis Uger, Canada. He is the incumbent of the Joseph Meyerhoff Professorial Chair of Biochemistry.
Prof. Silman's research was supported by the Nella and Leon Benoziyo Center for Neurosciences; the Charles A. Dana Foundation; the Carl and Micaela Einhorn-Dominic Brain Research Institute; and the Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly. He is the incumbent of the Bernstein-Mason Professorial Chair of Neurochemistry
Prof. Sussman's research was supported by the Charles A. Dana Foundation; the Jean and Jula Goldwurm Memorial Foundation; Mr. Yossi Hollander, Israel; the Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly; the Joseph and Ceil Mazer Center for Structural Biology; the late Sally Schnitzer; and the Kalman & Ida Wolens Foundation. He is the incumbent of the Morton and Gladys Pickman Chair in Structural Biology.
The research utilized infrastructure provided by the Kekst Family Center for Medical Genetics.