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In search of proof‐of‐concept: gene therapy for glycogen storage disease type Ia
Author(s) -
Koeberl Dwight D.
Publication year - 2012
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-012-9454-5
Subject(s) - genetic enhancement , glycogen storage disease , vector (molecular biology) , glycogen , transgene , hypoglycemia , viral vector , adeno associated virus , biology , glycogen storage disease type i , disease , gene , medicine , virology , bioinformatics , endocrinology , genetics , diabetes mellitus , recombinant dna
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.