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Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.

Publication ,  Journal Article
Crane, B; Luo, X; Demaster, A; Williams, KD; Kozink, DM; Zhang, P; Brown, TT; Pinto, CR; Oka, K; Sun, F; Jackson, MW; Chan, L; Koeberl, DD
Published in: Gene Ther
April 2012

Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia.

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Published In

Gene Ther

DOI

EISSN

1476-5462

Publication Date

April 2012

Volume

19

Issue

4

Start / End Page

443 / 452

Location

England

Related Subject Headings

  • Hypoglycemia
  • Glycogen Storage Disease Type I
  • Glucose-6-Phosphatase
  • Genetic Vectors
  • Genetic Therapy
  • Dogs
  • Dog Diseases
  • Body Weight
  • Biotechnology
  • Animals
 

Citation

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Crane, B., Luo, X., Demaster, A., Williams, K. D., Kozink, D. M., Zhang, P., … Koeberl, D. D. (2012). Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia. Gene Ther, 19(4), 443–452. https://doi.org/10.1038/gt.2011.86
Crane, B., X. Luo, A. Demaster, K. D. Williams, D. M. Kozink, P. Zhang, T. T. Brown, et al. “Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.Gene Ther 19, no. 4 (April 2012): 443–52. https://doi.org/10.1038/gt.2011.86.
Crane B, Luo X, Demaster A, Williams KD, Kozink DM, Zhang P, et al. Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia. Gene Ther. 2012 Apr;19(4):443–52.
Crane, B., et al. “Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.Gene Ther, vol. 19, no. 4, Apr. 2012, pp. 443–52. Pubmed, doi:10.1038/gt.2011.86.
Crane B, Luo X, Demaster A, Williams KD, Kozink DM, Zhang P, Brown TT, Pinto CR, Oka K, Sun F, Jackson MW, Chan L, Koeberl DD. Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia. Gene Ther. 2012 Apr;19(4):443–452.

Published In

Gene Ther

DOI

EISSN

1476-5462

Publication Date

April 2012

Volume

19

Issue

4

Start / End Page

443 / 452

Location

England

Related Subject Headings

  • Hypoglycemia
  • Glycogen Storage Disease Type I
  • Glucose-6-Phosphatase
  • Genetic Vectors
  • Genetic Therapy
  • Dogs
  • Dog Diseases
  • Body Weight
  • Biotechnology
  • Animals