The Pharmacological Chaperone AT2220 Increases Recombinant Human Acid α-Glucosidase Uptake and Glycogen Reduction in a Mouse Model of Pompe Disease
Figure 2
AT2220 increases the circulating half-life of rhGAA in rats.
(A) Eight-week old male Sprague Dawley rats were administered vehicle (water) or AT2220 (3 or 30 mg/kg) via oral gavage. Thirty minutes later, vehicle (saline) or rhGAA (10 mg/kg) was administered via bolus tail vein injection. Blood was collected at the indicated time points, and GAA activity (upper panel) and protein levels (lower panel) were measured in plasma as described in ‘Materials and Methods’. (B) Eight-week old male Sprague Dawley rats were administered vehicle (water) or AT2220 (3 or 30 mg/kg) via oral gavage. Thirty minutes later, vehicle (saline) or rhGAA (10 mg/kg) was administered via 60-minute intravenous infusion. Blood was collected at the indicated time points, and GAA activity (upper panel) and protein levels (lower panel) were measured in plasma. PS: post-start infusion; PE: post-end infusion. In both (A) and (B), each time point represents the mean±SEM of the activity measured from 3 rats; each lane on the Western blot contains plasma from a single rat, and is representative of two rats in each group.