Enzyme Replacement in Gaucher Disease 英文参考文献.docVIP

Open access, freely available online Research in Translation Enzyme Replacement in Gaucher Disease Ernest Beutler G aucher disease is the most common lysosomal storage disorder (Box 1). A de?ciency of translational medicine. At the same time, powerful commercial interests may have been in?uential in physicians adopting a high-dose rather than a low-dose treatment schedule. Moreover, the high cost of enzyme replacement therapy forces us to consider what society can afford in the way of palliative treatments for very rare diseases. of the enzyme glucocerebrosidase (Figure 1) causes accumulation of the glycolipid glucocerebroside in macrophages throughout the body. In the viscera, glucocerebroside arises mainly from the biodegradation of red and white blood cells. In the brain, glucocerebroside arises from the turnover of complex lipids during brain development and the formation of the myelin sheath of nerves. The disease may be discovered as an incidental ?nding in the elderly because of mild thrombocytopenia or splenomegaly, or it may present early in life with hepatosplenomegaly, thrombocytopenia, anemia, and bone lesions. The History of Enzyme Replacement Therapy The possibility that the therapeutic replacement of enzymes missing DOI: 10.1371/journal.pmed.0010021.g001 Figure 1. Glucocerebrosidase Cleaves a Linkage within Glucosylceramide, a Normal Intermediate in Glycolipid Metabolism from lysosomes could be achieved was ?rst raised by de Duve forty years ago when he wrote: “Any substance that is taken up intracellularly by an endocytic process is likely to end up within lysosomes. This obviously opens up many possibilities for interaction, including replacement therapy” [1]. Type 1 Gaucher disease, the most common type, seems a particularly suitable target for enzyme replacement therapy because of the lack of central nervous system involvement (visceral damage in Gaucher disease is reversible whereas the brain damage usually is not). By the 1970s, the underl