Molecular Approaches for the Treatment of Pompe Disease

Mol Neurobiol. 2020 Feb;57(2):1259-1280. doi: 10.1007/s12035-019-01820-5. Epub 2019 Nov 12.


Glycogen storage disease type II (GSDII, Pompe disease) is a rare metabolic disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme localized within lysosomes that is solely responsible for glycogen degradation in this compartment. The manifestations of GSDII are heterogeneous but are classified as early or late onset. The natural course of early-onset Pompe disease (EOPD) is severe and rapidly fatal if left untreated. Currently, one therapeutic approach, namely, enzyme replacement therapy, is available, but advances in molecular medicine approaches hold promise for even more effective therapeutic strategies. These approaches, which we review here, comprise splicing modification by antisense oligonucleotides, chaperone therapy, stop codon readthrough therapy, and the use of viral vectors to introduce wild-type genes. Considering the high rate at which innovations are translated from bench to bedside, it is reasonable to expect substantial improvements in the treatment of this illness in the foreseeable future.

Keywords: Alpha-glucosidase (GAA); Antisense oligonucleotides; GSDII; Gene therapy; Molecular therapy; Pompe disease; Therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Glycogen / metabolism*
  • Glycogen Storage Disease Type II / drug therapy*
  • Glycogen Storage Disease Type II / genetics
  • Humans
  • Lysosomes / drug effects*
  • Lysosomes / metabolism
  • Mutation / genetics
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • Phenotype
  • alpha-Glucosidases / drug effects
  • alpha-Glucosidases / genetics


  • Oligonucleotides, Antisense
  • Glycogen
  • alpha-Glucosidases