The potential action of galactose as a "chemical chaperone": increase of beta galactosidase activity in fibroblasts from an adult GM1-gangliosidosis patient.

[gm1 gangliosidosis]

The glycosphingolipid storage disorder GM 1 -gangliosidosis is a severe neurodegenerative condition for which no therapy is currently available . Protein misfolding in lysosomal defects may have the potential to be corrected by chemical chaperones : in vitro and clinical approaches are being investigated .We investigated the in vitro effect of galactose on some lysosomal hydrolases , and its in vitro efficacy as a chemical chaperone in GM 1 -gangliosidosis .Galactose was added to the culture medium of fibroblasts from patients , controls and transfected COS -1 cells . Enzyme assays of lysosomal hydrolases , beta galactosidase in particular , were performed .Our data show that galactose alters selectively alpha and beta galactosidases . A significant increase (2 ,5 fold ) in beta galactosidase activity occurred when galactose was added to the cultured fibroblasts of an adult patient . Chemical chaperone therapy requires the presence of residual enzyme activity . The adult patient here reported is heterozygous for the p .T 329 A mutation that showed no beta galactosidase activity , and for the p .R 442 Q mutation with residual enzyme activity . The p .R 442 Q mutation was therefore selected as a potential target for the galactose chaperone ; after the addition of galactose , COS -1 cells transfected with this mutation showed an increase in beta galactosidase activity from 6 .9 % to 12 % of control values .These results suggest that galactose or its derivatives with potential chaperone properties could be used in the development of non-invasive therapies for GM 1 -gangliosidosis .