Galactonojirimycin derivatives restore mutant human β-galactosidase activities expressed in fibroblasts from enzyme-deficient knockout mouse

Ten low molecular compounds analogous to galactose were screened for inhibition of human β-galactosidase activity. Among them, 1-deoxy-galactonojirimycin and N-(n-butyl)-deoxy-galactonojirimycin showed an inhibitory effect at high concentrations. However, they restored mutant enzyme activities expressed in enzyme-deficient knockout mouse fibroblasts and human β-galactosidosis fibroblasts at lower intracellular concentrations. This effect was more remarkable on GM1-gangliosidosis mutations (R201C, I51T, R201H, R457Q) than Morquio B disease mutations (W273L, Y83H). These low molecular compounds pass though the blood–brain barrier in mice. We hope that this new therapeutic approach will become clinically applicable in the near future.