Immunomodulatory, liver depot gene therapy for Pompe disease.

Journal Article (Journal Article;Review)

Pompe disease is caused by mutations in acid alpha glucosidase (GAA) that causes accumulation of lysosomal glycogen affecting the heart and skeletal muscles, and can be fatal. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) improves muscle function by reducing glycogen accumulation. Limitations of ERT include a short half-life and the formation of antibodies that result in reduced efficacy. By harnessing the immune tolerance induction properties of the liver, liver-targeted gene delivery (with an adeno-associated virus vector containing a liver specific promoter), suppresses immunity against the GAA introduced by gene therapy. This induces immune tolerance to rhGAA by activating regulatory T cells and simultaneously, corrects GAA deficiency. Potentially, liver-targeted gene therapy can be performed once with lasting effects, by administering a relatively low dose of an adeno-associated virus type 8 vector to replace and induce immune tolerance to GAA.

Full Text

Duke Authors

Cited Authors

  • Bond, JE; Kishnani, PS; Koeberl, DD

Published Date

  • August 2019

Published In

Volume / Issue

  • 342 /

Start / End Page

  • 103737 -

PubMed ID

  • 29295737

Pubmed Central ID

  • PMC6026080

Electronic International Standard Serial Number (EISSN)

  • 1090-2163

Digital Object Identifier (DOI)

  • 10.1016/j.cellimm.2017.12.011


  • eng

Conference Location

  • Netherlands