Macrophage Models of Gaucher Disease for Evaluating Disease Pathogenesis and Candidate Drugs

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Science Translational Medicine  11 Jun 2014:
Vol. 6, Issue 240, pp. 240ra73
DOI: 10.1126/scitranslmed.3008659

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Emptying the Trash

Studies of Gaucher disease, caused by a deficiency of the enzyme glucocerebrosidase, have been hindered by the lack of cellular models that show glycolipid accumulation in the lysosomes of macrophages, a hallmark characteristic of the disease. Using blood and skin samples from patients with Gaucher disease, Aflaki et al. now have developed macrophage models that recapitulate characteristics of the disease, including loss of glucocerebrosidase activity, glycolipid accumulation in lysosomes, and impaired macrophage function. Treatment of patient-derived macrophages with a new small-molecule drug corrected the enzyme deficiency, reduced lysosomal storage of lipids, and restored macrophage function. These new cellular models of Gaucher disease should facilitate our understanding of this disorder and the development of new drugs.