AAV-Vectors for Treatment of Glycogen Storage Disorders

Adeno-Associated Virus Vectors for the treatment of glycogen storage disease, particularly glycogen storage disease type Ia, are disclosed. Glycogen storage disease type Ia (GSD-Ia or von Gierke disease) is caused by a deficiency in glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC). Patients affected by GSD-Ia are unable to maintain glucose homeostasis and present with fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic academia. There is currently no cure for GSD-Ia deficiency disorder. NIH investigators have constructed a novel gene therapy vector by placing the G6PC gene in a novel virus-based vector, named ssAAV-G6PC-GPE. The expression of G6Pase-alpha in ssAAV-G6PC-GPE is directed by the human G6PC promoter/enhancer at nucleotides -2864 to -1 (GPE) and this vector also contains an intron. The G6pc-/- mice treated with ssAAV-G6PC-GPE vector exhibited normal levels of blood glucose, blood metabolites, hepatic glycogen, and hepatic fat. This vector was compared with a dsAAV-G6Pase vector which differed from the NIH vector that it is double stranded and contained much smaller G6PC promoter. The results showed that the ssAAV-G6PC-GPE vector directed significantly higher expression of G6Pase-alpha and achieved greater reduction in hepatic glycogen storage while better tolerating fasting conditions. The results also showed that the enhancer elements upstream the human G6PC minimal promoter contained within the ssAAV-G6PC-GPE vector are responsible for the increased efficacy in treating GSD-Ia mice.

Potential Commercial Applications: Competitive Advantages:
  • Gene therapy for glycogen storage disorders, specifically caused by the deficiency of G6Pase-alpha.
  • Comparative studies showed that the ssAAV-G6Pase-GPE vector is more efficacious than other candidate therapy vectors.

Development Stage:
  • In vitro data available
  • In vivo data available (animal)


Janice Chou (NICHD)  ➽ more inventions...

Intellectual Property:
U.S. Pat: 9,644,216 issued 2017-05-09
US Application No. 61/908,861
PCT Application No. PCT/US2014/067415
US Application No. 15/493,622
US Application No. 16/148,435

Lee YM, et al. PMID 23856420

Licensing Contact:
Surekha Vathyam, Ph.D.
Email: vathyams@mail.nih.gov
Phone: 240-276-6865

OTT Reference No: E-552-2013-0
Updated: Aug 6, 2014