Waltham, MABrandeis 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
Contact: Laura Gardner