A Genetic Disease
Gaucher's disease is the most common genetic disease among the Ashkenazi Jewish population of Eastern European ancestry. Symptoms include bruising easily due to low blood platelets, enlargement of the liver and spleen, and 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, sometimes resulting in painful fractures. In some instances, the disease also impairs the function of the lungs or the central nervous system.
Gaucher's disease (named after the French dermatologist Phillipe Gaucher, who first described the condition in 1882) is caused by mutations in a person's beta-glucosidase genes, and these defects corrupt his or her beta-glucosidase enzyme. Some of these corrupted enzymes cannot fold properly into their correct three-dimensional structure because they are unstable in the neutral pH environment of the endoplasmic reticulum. The corrupted, mutant enzymes are often degraded by a process known as endoplasmic reticulum-associated degradation, and fail to reach their destinationanother subcellular compartment called the lysosome, where they normally break down a fatty substance called glucosylceramides. When the beta-glucosidase concentration and/or enzymatic activity in the lysosome are too low, glucosylceramides accumulate, causing the symptoms of Gaucher's disease.
The current approaches for treating Gaucher's disease (and a few of the 40 or so other lysosomal storage disorders) involve replacing the deficient enzyme with an enzyme that is made using recombinant engineering and then is injected into the patient. Enzyme replacement therapy is an effective way to restore many patients to good health, but it has drawbacks. The enzyme has to be infused intravenously or through a surgically implanted catheterusually in a doctor's officea process tha
|Contact: Keith McKeown|
Scripps Research Institute