GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused 
by a genetic deficiency of acid beta-galactosidase (beta-gal), the enzyme that 
catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) 
occurs primarily in the brain, leading to progressive neurodegeneration and 
brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL 
biosynthesis to counterbalance the impaired rate of catabolism. The imino sugar 
N-butyldeoxygalactonojirimycin (NB-DGJ) is a competitive inhibitor of the 
ceramide-specific glucosyltransferase that catalyzes the first step in GSL 
biosynthesis. Neonatal C57BL/6J (B6) and beta-gal knockout (-/-) mice were 
injected daily from post-natal day 2 (p-2) to p-5 with either vehicle or NB-DGJ 
at 600 mg or 1200 mg/kg body weight. These drug concentrations significantly 
reduced total brain ganglioside and GM1 content in the B6 and the beta-gal (-/-) 
mice. Drug treatment had no significant effect on viability, body weight, brain 
weight, or brain water content in the B6 and beta-gal (-/-) mice. Significant 
elevations in neutral lipids (GA1, ceramide, and sphingomyelin) were observed in 
the NB-DGJ-treated beta-gal (-/-) mice, but were not associated with adverse 
effects. Also, NB-DGJ treatment of B6 and beta-gal (-/-) mice from p-2 to p-5 
had no subsequent effect on brain ganglioside content at p-21. Our results show 
that NB-DGJ is effective in reducing total brain ganglioside and GM1 content at 
early neonatal ages. These findings suggest that substrate reduction therapy 
using NB-DGJ may be an effective early intervention for GM1 gangliosidosis and 
possibly other GSL lysosomal storage diseases.