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Effective enzyme replacement therapy of type I Gaucher disease, based on chronic intravenous administration of mannose\u2010terminated recombinant human glucocerebrosidase, has been available since 1990 and has been applied in several thousand patients without serious adverse effects. An alternative therapeutic approach, so\u2010called substrate reduction therapy, is based on partial reduction of the synthesis of glucosylceramide and hence of subsequent metabolites. Oral administration of an inhibitor of glucosylceramide synthesis (<jats:italic>N<\/jats:italic>\u2010butyldeoxynojirimycin, registered in Europe since 2002 as miglustat (Zavesca)), is effective in reversing clinical symptoms in type I Gaucher patients with mild to moderate disease manifestations. The growing long\u2010term experience with substrate reduction therapy indicates that this treatment is also without major adverse effects. Substrate reduction therapy, in conjunction with enzyme replacement therapy, may play an important role in the future clinical management of patients suffering from type I Gaucher disease. Clinical trials are under way that should reveal the value of substrate reduction for maintenance therapy of type I Gaucher disease and for treatment of neuronopathic variants of Gaucher disease, Niemann\u2013Pick disease type C, late\u2010onset Tay\u2013Sachs disease and Sandhoff disease.<\/jats:p>","DOI":"10.1007\/s10545-006-0272-5","type":"journal-article","created":{"date-parts":[[2006,6,9]],"date-time":"2006-06-09T03:09:10Z","timestamp":1149822550000},"page":"449-456","source":"Crossref","is-referenced-by-count":120,"title":["Substrate reduction therapy of glycosphingolipid storage disorders"],"prefix":"10.1002","volume":"29","author":[{"given":"Johannes M. F. 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