The Pharmacological Chaperone AT2220 Increases Recombinant Human Acid α-Glucosidase Uptake and Glycogen Reduction in a Mouse Model of Pompe Disease
Figure 4
Co-administration of AT2220 promotes greater tissue uptake of rhGAA in GAA KO mice.
Twelve-week old male GAA KO mice were administered vehicle (water) or AT2220 (30 mg/kg) via oral gavage once every other week for 8 weeks. Thirty minutes after each AT2220 oral administration, vehicle (saline) or rhGAA (20 mg/kg) was administered via bolus tail vein injection. Mice were euthanized 7 days after the last (i.e., 4th) rhGAA administration and tissue GAA activity was measured as described in ‘Materials and Methods’. Each bar represents the mean±SEM of the GAA activity measured from 5 mice per group. Statistically significant increases were seen in GAA activity compared to baseline (*p<0.05, t-test) and compared to rhGAA administration alone (#p<0.05, t-test). For comparison, GAA levels in wild-type C57BL/6 mice were 15±2, 16±0.6, 21±3, 18±2, 11±2, and 25±3 nmol/mg protein/hr in heart, diaphragm, gastrocnemius, quadriceps, triceps, and tongue, respectively (mean±SEM of 7 mice).