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Laura Gardner

Technology for Gaucher Disease

WALTHAM, Mass. (Feb. 22, 2007) — Brandeis University and Brigham and Women’s Hospital today agreed to grant a license option to Amicus Therapeutics for a jointly-developed novel pharmaceutical technology that could be instrumental in finding new treatments for Gaucher Disease. Biochemists Raquel Lieberman, Gregory Petsko and Dagmar Ringe, each affiliated with both Brandeis and Brigham and Women’s, invented a patentable technology related to the structure of acid beta-glucosidase, also known as GCase, and methods for identifying therapeutic agents. In collaboration with scientists at Amicus Therapeutics, the inventors discovered that GCase, the protein that is mutated in Gaucher Disease, undergoes a structural change near its active site upon binding to a small molecule that is in clinical trials for the treatment of the disease.

One emerging type of treatment for genetic diseases such as Gaucher Disease involves the use of small molecules known as pharmacological chaperones, which are proposed to help mutated, less stable proteins perform their normal function in the cells of patients with the disease. The identification of appropriate pharmacological chaperones and understanding how they work in the body are aided by knowing the structure of the target protein under different conditions and when bound to the small molecule.

Cranbury, New Jersey-based Amicus Therapeutics, which specializes in the discovery and development of pharmacological chaperones, will use this structure of GCase to look for additional small molecules that can keep the protein properly folded and stabilized.

“This work helps explain the way pharmacological chaperones work to stabilize proteins that are rendered less stable by genetic mutations in diseases such as Gaucher, Anderson-Fabry, and other genetic disorders,” explained Petsko, the Gyula and Katica Tauber Professor of Biochemistry and Chemistry, Brandeis University and Adjunct Professor, Department of Neurology and Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School. “With this information it may be possible to use the pharmacological chaperone strategy in other diseases.”

About Gaucher Disease
Gaucher Disease is an often devastating genetic disorder that may afflict up to one in every five hundred persons, but as many as one in fifteen in the Ashkenazi Jewish population. Gaucher Disease is an inborn error of metabolism that arises from the inability of cells to hydrolyze a particular lipid, leading to liver dysfunction and damage to the spleen and skeleton, among other serious problems. Although there are dozens of genetic mutations known to cause Gaucher Disease, just four mutations are responsible for 95 percent of the cases among Ashkenazi Jews and 50 percent of the cases in the general population.

About Amicus Therapeutics
Amicus Therapeutics is a biopharmaceutical company developing novel, oral therapeutics known as pharmacological chaperones for the treatment of a range of human genetic diseases. Pharmacological chaperone technology involves the use of small molecules to restore or improve biological activity in cells by selectively binding to misfolded proteins caused by genetic mutations. Amicus is initially targeting lysosomal storage disorders, which are severe, chronic genetic diseases with unmet medical needs. Amicus is currently conducting Phase 2 clinical trials for its lead compound, Amigal™, for Fabry disease, has completed Phase 1 clinical trials of AT2101 for Gaucher disease and is conducting Phase 1 clinical trials of AT2220 for Pompe disease.