Research ArticleGene Therapy

Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase

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Science Translational Medicine  29 Nov 2017:
Vol. 9, Issue 418, eaam6375
DOI: 10.1126/scitranslmed.aam6375

Revealing a secretable GAA for Pompe disease

Pompe disease is a genetic disorder caused by mutations in the acid α-glucosidase (GAA) gene, leading to glycogen accumulation in all cells of the body. This accumulation leads to severe neuromuscular disabilities that can be life-threatening. Puzzo et al. used bioinformatic analysis, protein engineering, and gene therapy to develop and deliver a GAA transgene encoding a secretable GAA. Liver-specific, adeno-associated virus (AAV) vector–mediated GAA delivery rescued the Pompe disease phenotype in a mouse model and increased GAA expression in healthy monkeys, opening possibilities for future translation of this approach for treating Pompe disease.

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