caa a22 4500 467933189 CHVBK 20180406152949.0 cr unu---uuuuu 170328e20060401xx s 000 0 eng 10.1007/s10545-006-0272-5 doi (NATIONALLICENCE)springer-10.1007/s10545-006-0272-5 Substrate reduction therapy of glycosphingolipid storage disorders [Elektronische Daten] [Johannes Aerts, Carla Hollak, Rolf Boot, Johanna Groener, Mario Maas] Summary: In the last 15 years enormous progress has been made regarding therapy of type I Gaucher disease, a severely disabling disorder characterized by intralysosomal storage of glucosylceramide in tissue macrophages. Effective enzyme replacement therapy of type I Gaucher disease, based on chronic intravenous administration of mannose-terminated 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-called 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 (N-butyldeoxynojirimycin, 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-term 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-Pick disease type C, late-onset Tay-Sachs disease and Sandhoff disease. SSIEM and Springer, 2006 Aerts Johannes Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands aut Hollak Carla Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands aut Boot Rolf Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands aut Groener Johanna Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands aut Maas Mario Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/2-3(2006-04-01), 449-456 0141-8955 29:2-3<449 2006 29 10545 https://doi.org/10.1007/s10545-006-0272-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0272-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Aerts Johannes Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Hollak Carla Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Boot Rolf Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Groener Johanna Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Maas Mario Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/2-3(2006-04-01), 449-456 0141-8955 29:2-3<449 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer