In search of proof-of-concept: gene therapy for glycogen storage disease type Ia.

Abstract

The emergence of life threatening long-term complications in glycogen storage disease type Ia (GSD-Ia) has emphasized the need for new therapies, such as gene therapy, which could achieve biochemical correction of glucose-6-phosphatase deficiency and reverse clinical involvement. We have developed gene therapy with a novel adeno-associated virus (AAV) vector that: 1) prevented mortality and corrected glycogen storage in the liver, 2) corrected hypoglycemia during fasting, and 3) achieved efficacy with a low number of vector particles in G6Pase-deficient mice and dogs. However, the gradual loss of transgene expression from episomal AAV vector genomes eventually necessitated the administration of a different pseudotype of the AAV vector to sustain dogs with GSD-Ia. Further preclinical development of AAV vector-mediated gene therapy is therefore warranted in GSD-Ia.

• Authors: Dwight D Koeberl
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 35 Issue 4 Pg. 671-8 (Jul 2012) ISSN: 1573-2665 [Electronic] United States
• PMID: 22310927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Dependovirus (genetics)
• Genetic Therapy (methods)
• Genetic Vectors (genetics)
• Glycogen Storage Disease Type I (genetics, metabolism, therapy)
• Humans