Gene therapy for glycogen storage diseases

Hum Mol Genet. 2019 Oct 1;28(R1):R31-R41. doi: 10.1093/hmg/ddz133.


The focus of this review is the development of gene therapy for glycogen storage diseases (GSDs). GSD results from the deficiency of specific enzymes involved in the storage and retrieval of glucose in the body. Broadly, GSDs can be divided into types that affect liver or muscle or both tissues. For example, glucose-6-phosphatase (G6Pase) deficiency in GSD type Ia (GSD Ia) affects primarily the liver and kidney, while acid α-glucosidase (GAA) deficiency in GSD II causes primarily muscle disease. The lack of specific therapy for the GSDs has driven efforts to develop new therapies for these conditions. Gene therapy needs to replace deficient enzymes in target tissues, which has guided the planning of gene therapy experiments. Gene therapy with adeno-associated virus (AAV) vectors has demonstrated appropriate tropism for target tissues, including the liver, heart and skeletal muscle in animal models for GSD. AAV vectors transduced liver and kidney in GSD Ia and striated muscle in GSD II mice to replace the deficient enzyme in each disease. Gene therapy has been advanced to early phase clinical trials for the replacement of G6Pase in GSD Ia and GAA in GSD II (Pompe disease). Other GSDs have been treated in proof-of-concept studies, including GSD III, IV and V. The future of gene therapy appears promising for the GSDs, promising to provide more efficacious therapy for these disorders in the foreseeable future.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Gene Editing
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genetic Therapy* / adverse effects
  • Genetic Therapy* / methods
  • Genetic Vectors / genetics
  • Glycogen Storage Disease / genetics*
  • Glycogen Storage Disease / metabolism
  • Glycogen Storage Disease / therapy*
  • Humans
  • Immunomodulation
  • Liver / metabolism
  • Organ Specificity
  • Standard of Care
  • Transduction, Genetic
  • Transgenes
  • Treatment Outcome


  • Biomarkers