Fig. 8: Pharmacological chaperones enhance gene therapy efficacy.

A Experimental design. 4-month-old Gaa^−/−Cd4^−/− mice received a single injection of AAV-GAA at 1 × 10¹¹ vg/kg with or without a regimen of 1-Deoxynojirimycin (DNJ) and ambroxol (ABX) given at 3 days on followed by 3 days off intervals. Untreated Gaa^+/+Cd4^−/− and Gaa^−/−Cd4^−/− mice were used as controls. B Analysis of GAA activity in blood. C Western blot analysis of circulating GAA protein. D Quantification of circulating GAA protein bands in B. Analysis of GAA activity (E) and glycogen content (F) in muscles at the end of the study. G Heart weight expressed as percentage of body weight. H Analysis of grip strength 2 months after treatment. Data shown as average ± SD. Statistical analysis: B Two-way ANOVA with Tukey post-hoc test; D t-test; E–H One-way ANOVA with Tukey post-hoc test *, ^† and ^# p < 0.05; **, ^†† and ^## p < 0.01; ***, ^††† and ^### p < 0.001; ****, ^†††† and ^#### p < 0.0001. Exact p values for B, E–H are provided in the Source Data file. B–H: n = 8 mice per treatment group.