Figure 1.

Liver Expression of Secretable GAA Rescues Pompe Disease at Low Vector Doses

(A–F) 4-month-old Gaa^−/− mice were injected with an AAV8-GAAco (GAAco-Gaa^−/−) or AAV8-secGAA (secGAA-Gaa^−/−) vector at a dose of 5 × 10¹¹ vg/kg. Gaa^+/+ (PBS-Gaa^+/+) and Gaa^−/− (PBS-Gaa^−/−) mice injected with PBS served as controls in the study. Animals were followed for 10 months after treatment (n = 7/8 per cohort). (A) Graphical representation of the study design (m.o., months old). (B) Survival curve. The numbers in parentheses show the number of animals survived at the end of the study. (C) Hypertrophy of cardiac muscle, reported as heart weight percentage of body mass. (D) Muscle strength tested by grip test at 3, 6, and 9 months post-treatment, presented as percentage of PBS-Gaa^+/+. (E and F) GAA enzymatic activity (E) and glycogen content (F) in diaphragm. Statistical analyses: (B) Kaplan-Meier log rank test. ∗p < 0.05; (C, E, and F) one-way ANOVA with Tukey’s post hoc. ns, not significant. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001; (D) two-way ANOVA time per treatment. +p < 0.05; ∗∗, ++, or ##p < 0.01; +++p < 0.001; ++++ or ∗∗∗∗p < 0.0001. In all graphs, error bars represent the standard deviation of the mean.