PREVENTION OF LYSOSOMAL STORAGE IN TAY-SACHS MICE TREATED WITH N-BUTYLDEOXYNOJIRIMYCIN

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-butyldeoxy nojirimycin, was evaluated in a mouse model of Tay-Sachs disease. When Tay-Sachs mice were treated with N-butyldeoxynojirimycin, the accumul ation of G(M2) in the brain was prevented, with the number of storage neurons and the quantity of ganglioside stored per cell markedly reduc ed. Thus, limiting the biosynthesis of the substrate (G(M2)) for the d efective enzyme (beta-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage.