American Association for the Advancement of Science, Science, 5311(276), p. 428-431, 1997
DOI: 10.1126/science.276.5311.428
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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 G M2 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 (G M2 ) for the defective enzyme (β-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.