What's new and what's next for gene therapy in Pompe disease?

Expert Opin Biol Ther. 2022 Sep;22(9):1117-1135. doi: 10.1080/14712598.2022.2067476. Epub 2022 Apr 27.


Introduction: Pompe disease is an autosomal recessive disorder caused by a deficiency of acid-α-glucosidase (GAA), an enzyme responsible for hydrolyzing lysosomal glycogen. A lack of GAA leads to accumulation of glycogen in the lysosomes of cardiac, skeletal, and smooth muscle cells, as well as in the central and peripheral nervous system. Enzyme replacement therapy has been the standard of care for 15 years and slows disease progression, particularly in the heart, and improves survival. However, there are limitations of ERT success, which gene therapy can overcome.

Areas covered: Gene therapy offers several advantages including prolonged and consistent GAA expression and correction of skeletal muscle as well as the critical CNS pathology. We provide a systematic review of the preclinical and clinical outcomes of adeno-associated viral mediated gene therapy and alternative gene therapy strategies, highlighting what has been successful.

Expert opinion: Although the preclinical and clinical studies so far have been promising, barriers exist that need to be addressed in gene therapy for Pompe disease. New strategies including novel capsids for better targeting, optimized DNA vectors, and adjuctive therapies will allow for a lower dose, and ameliorate the immune response.

Keywords: AAV; GAA; Pompe disease; acid alpha-glucosidase; gene therapy; neuromuscular disorder.

Publication types

  • Systematic Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Therapy
  • Glycogen / metabolism
  • Glycogen / therapeutic use
  • Glycogen Storage Disease Type II* / genetics
  • Glycogen Storage Disease Type II* / pathology
  • Glycogen Storage Disease Type II* / therapy
  • Humans
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • alpha-Glucosidases / genetics
  • alpha-Glucosidases / metabolism
  • alpha-Glucosidases / therapeutic use


  • Glycogen
  • alpha-Glucosidases