Alglucosidase alfa

Alglucosidase alfa (rhGAA) is a recombinant human acid α-glucosidase. Alglucosidase alfa is taken up by cells via the cation-independent mannose-6-phosphate receptor (CI-MPR) pathway and transported to lysosomes, where GAA degrades glycogen in the acidic lysosomal environment. Alglucosidase alfa is applicable to research related to lysosomal glycogen metabolism and glycogen storage diseases^{[1][2][3][4][5]}.
In Vivo:Alglucosidase alfa (rhGAA) (20 mg/kg; intravenous injection; once every two weeks; 2 doses total) reduces glycogen accumulation in the quadriceps, gastrocnemius, triceps brachii, and heart of male Gaa-KO mice at approximately 16 weeks of age^[1].
Neither alglucosidase alfa (120 µg; intracranial injection; single dose; analyzed 7 days post-injection) nor alglucosidase alfa (13.2-17.2 µg/day; intracranial injection; continuous infusion; 14-30 days) reduces the number of Lafora bodies, brain glycogen levels, or improves behavioral outcomes in Epm2a^-/- knockout mice with Lafora disease^[2].
Alglucosidase alfa (40 mg/kg; i.v.; once weekly; 4 weeks) reduces hepatic glycogen accumulation by 21% in GSD IV mice, but does not significantly decrease glycogen in skeletal muscle; a dose of 20 mg/kg does not produce a significant reduction in glycogen accumulation in the tested tissues^[4].
Long-term administration of alglucosidase alfa (20 mg/kg; intravenous injection; once every two weeks; 2 doses total) fails to improve muscle function, myofiber size, or dysferlin localization in Gaa-KO mice^[1].
Following administration of alglucosidase alfa (20 mg/kg; i.v.; once every 2 weeks, for a total of 4 doses), extensive Lamp1/LC3-positive autophagic accumulation remains in the muscle fibers of Gaa-KO mice, with over 95% of the examined muscle fibers still containing such autophagic accumulation^[1].
Alglucosidase alfa (20 mg/kg; i.v.; weekly; 12 weeks) induces anti-rhGAA-specific IgG responses in E4-8GAAKO Pompe mice; upon re-exposure after a 4-week withdrawal, the antibody response is further elevated in the rhGAA-alone group, whereas the group receiving combined treatment with low-dose Methotrexate (HY-14519) maintains low antibody levels^[3].
Alglucosidase alfa (20 or 40 mg/kg; i.v.; once weekly; 4 weeks) dose-dependently increases GAA activity in multiple tissues of Gbe1^ys/ys GSD IV mice; GAA activity in the liver increases by 29-fold and 48-fold in the 20 mg/kg and 40 mg/kg groups, respectively, while that in the heart increases by 1.7-fold and 2.8-fold, respectively, with only a slight increase observed in the quadriceps femoris^[4].