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Science 18 April 1997:
Vol. 276. no. 5311, pp. 428 - 431
DOI: 10.1126/science.276.5311.428
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Reports

Prevention of Lysosomal Storage in Tay-Sachs Mice Treated with N-Butyldeoxynojirimycin

Frances M. Platt, * Gabrielle R. Neises, Gabriele Reinkensmeier, Mandy J. Townsend, V. Hugh Perry, Richard L. Proia, Bryan Winchester, Raymond A. Dwek, Terry D. Butters

The glycosphingolipid (GSL) lysosomal storage diseases result from the inheritance of defects in the genes encoding the enzymes required for catabolism of GSLs within lysosomes. A strategy for the treatment of these diseases, based on an inhibitor of GSL biosynthesis N-butyldeoxynojirimycin, was evaluated in a mouse model of Tay-Sachs disease. When Tay-Sachs mice were treated with N-butyldeoxynojirimycin, the accumulation of GM2 in the brain was prevented, with the number of storage neurons and the quantity of ganglioside stored per cell markedly reduced. Thus, limiting the biosynthesis of the substrate (GM2) for the defective enzyme (beta -hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.

F. M. Platt, G. Reinkensmeier, R. A. Dwek, T. D. Butters, Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford 0X1 3QU, UK.
G. R. Neises, Monsanto Company, 700 Chesterfield Village Parkway, St. Louis, MO 63198, USA.
M. J. Townsend and V. H. Perry, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
R. L. Proia, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
B. Winchester, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
*   To whom correspondence should be addressed. E-mail: fran{at}oxglua.glycob.ox.ac.uk

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