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Glucose-6-phosphate transporter gene therapy corrects metabolic and myeloid abnormalities in glycogen storage disease type Ib mice

Gene Therapy volume 14, pages 219–226 (2007)Cite this article

Abstract

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT), an endoplasmic reticulum-associated transmembrane protein that is ubiquitously expressed. GSD-Ib patients suffer from disturbed glucose homeostasis and myeloid dysfunctions. To evaluate the feasibility of gene replacement therapy for GSD-Ib, we have infused adenoviral (Ad) vector containing human G6PT (Ad-hG6PT) into G6PT-deficient (G6PT−/−) mice that manifest symptoms characteristics of the human disorder. Ad-hG6PT infusion restores significant levels of G6PT mRNA expression in the liver, bone marrow and spleen, and corrects metabolic as well as myeloid abnormalities in G6PT−/− mice. The G6PT−/− mice receiving gene therapy exhibit improved growth; normalized serum profiles for glucose, cholesterol, triglyceride, uric acid and lactic acid; and reduced hepatic glycogen deposition. The therapy also corrects neutropenia and lowers the elevated serum levels of granulocyte colony-stimulating factor. The development of bone and spleen in the infused G6PT−/− mice is improved and accompanied by increased cellularity and normalized myeloid progenitor cell frequencies in both tissues. This effective use of gene therapy to correct metabolic imbalances and myeloid dysfunctions in GSD-Ib mice holds promise for the future of gene therapy in humans.

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Acknowledgements

We thank Dr Brian C Mansfield for critical reading of the paper.

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Authors and Affiliations

  1. Heritable Disorders Branch, Section on Cellular Differentiation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    W H Yiu, C-J Pan, M Allamarvdasht, S Y Kim & J Y Chou

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  1. W H Yiu
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Correspondence to J Y Chou.

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Yiu, W., Pan, CJ., Allamarvdasht, M. et al. Glucose-6-phosphate transporter gene therapy corrects metabolic and myeloid abnormalities in glycogen storage disease type Ib mice. Gene Ther 14, 219–226 (2007). https://doi.org/10.1038/sj.gt.3302869

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