Correction of glycogen storage disease type III with AAV vectors


Glycogen storage disease type III (GSDIII) is an autosomal recessive disorder caused by a deficiency of glycogen-debranching enzyme (GDE), which results in profound liver metabolism impairment and muscle weakness. To date, no cure is available for GSDIII and current treatments are mostly based on diet. Here, the authors describe the development of a mouse model of GSDIII, which faithfully recapitulates the main features of the human condition. This model was used to develop and test novel therapies based on adeno-associated virus (AAV) vector-mediated gene transfer. Their results provide proof of concept of correction of GSDIII with AAV vectors, and indicate that restoration of the enzyme deficiency in muscle and liver is necessary to address both the metabolic and neuromuscular manifestations of the disease.

Vidal P, Pagliarani S, Colella P, et al. Rescue of GSDIII Phenotype with Gene Transfer Requires Liver- and Muscle-Targeted GDE Expression. Mol Ther. 2017 Dec 28. pii: S1525-0016(17)30616-0. [Epub ahead of print]