Patients with Gaucher disease may bruise easily due to low blood platelets, and they may have enlargement of the liver and spleen. Sometimes they experience fatigue due to anemia. The disease also causes cells in the bone marrow to become engorged with a fatty storage material, which may lead to bone lesions, weakening the skeleton, and sometimes resulting in painful fractures. In some instances, the disease also impairs the function of the lungs.
In an article that will be published in an upcoming issue of the journal Proceedings of the National Academy of Sciences, the TSRI group describes using small molecules to partially correct the genetic defect that underlies most cases of Gaucher disease. The defect prevents a crucial metabolic enzyme from reaching the location in the cell where it normally functions, but the small molecules act as "chaperones," guiding the mutant enzyme to the right location and allowing it to survive and function.
"This is an entirely new approach to the disease," says TSRI Professor Ernest Beutler, M.D., who is one of the authors of the study and one of the world's leading experts on Gaucher disease and similar metabolic disorders. Beutler's laboratory was the first to clone the gene responsible for Gaucher disease in the mid-1980s.
"And it may be less costly and more convenient than the current treatment," adds Jeffrey W. Kelly, who is the Lita Annenberg Hazen Professor of Chemistry and vice president of academic affairs at TSRI. Kelly led the research effort along with the study's first author, Anu Sawkar, a Ph.D. student in
Contact: Jason Bardi
Scripps Research Institute