Figure 2.

secGAA Normalizes Muscle Phenotype in Advanced Stages of Pompe Disease

(A–G) 9-month-old mice were injected with an AAV8-secGAA (secGAA-Gaa^−/−) vector at a dose of 2 × 10¹² vg/kg. Gaa^+/+ (PBS-Gaa^+/+) and Gaa^−/− (PBS-Gaa^−/−) mice injected with PBS served as controls in the study. Animals were followed for 9 months after treatment (n = 3/4 per cohort). (A) Graphical representation of the study design (m.o., months old). (B) GAA enzymatic activity measured in plasma at 1, 3, 6, and 9 months postinjection. (C) GAA enzymatic activity in heart, diaphragm, and triceps muscles, reported as percentage of PBS-Gaa^+/+ activity. (D) Glycogen content in heart, diaphragm, and triceps muscles, reported as percentage of PBS-Gaa^−/− glycogen. (E) Hypertrophy of cardiac muscle, reported as heart weight percentage of body mass. (F) Grip-test analysis reported as percentage of PBS-Gaa^+/+ muscle strength. (G) Tidal volume measured by whole-body plethysmography. Statistical analyses: (B, E, and G) one-way ANOVA with Tukey’s post hoc. ∗∗p < 0.01; (C and D) two-way ANOVA with Tukey’s post hoc (treatment, tissue). ∗p < 0.05; ∗∗p < 0.01; ∗∗∗∗p < 0.0001; (F) two-way ANOVA with Tukey’s post hoc (treatment, time). #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.