Alglucosidase alfa treatment alleviates liver disease in a mouse model of glycogen storage disease type IV

Abstract

Patients with progressive hepatic form of GSD IV often die of liver failure in early childhood. We tested the feasibility of using recombinant human acid-α glucosidase (rhGAA) for treating GSD IV. Weekly intravenously injection of rhGAA at 40 mg/kg for 4 weeks significantly reduced hepatic glycogen accumulation, lowered liver/body weight ratio, and reduced plasma ALP and ALT activities in GSD IV mice. Our data suggests that rhGAA is a potential therapy for GSD IV.

The potential of dietary treatment in patients with glycogen storage disease type IV

“…To conclude, this study demonstrates the potential of dietary management in a subset of GSD IV patients, as it should be considered in clinically stable patients prior to pursuing LT. This is particularly important as new treatments are being investigated for the hepatic glycogen storage diseases, including GSD IV, such as pharmacologic therapies, 32 gene therapy, 33 base editing, 34 RNA inhibition, 35 and mRNA therapy 36 …”

Alleviation of a polyglucosan storage disorder by enhancement of autophagic glycogen catabolism

“…Alternatively, spacing of the lysosomal membrane by LAMP1‐KD/144DG11 may enable glycogen import to the lysosome (and consequent degradation) by the STBD1 protein (Sun et al , 2016). Importantly, lysosomal glycogen degradation takes place in parallel with its cytoplasmic degradation (Adeva‐Andany et al , 2016) and, specifically, in a GSDIV mouse model, which also models APBD in mice, treatment with the recombinant human lysosomal enzyme acid α‐glucosidase alleviated disease in the liver (Yi et al , 2016).…”