GSD-Ia is an inherited disorder of metabolism associated with life-threatening hypoglycemia, hepatic malignancy, and renal failure caused by the deficiency of glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC). Current therapy, which primarily consists of dietary modification, fails to prevent long-term complications in many patients, including growth failure, gout, pulmonary hypertension, renal dysfunction, osteoporosis, and hepatocellular adenomas (HCA). Gene therapy-based techniques, which directly address the underlying genetic deficiency driving the disorder, offer the prospect of long-term remission in patients with GSD-Ia.
Researchers at the NIH National Institute for Child Health and Human Development developed adeno-associated viral (AAV) vectors for the treatment of glycogen storage disease type Ia (GSD-Ia).This technology describes new AAV vectors for the delivery of corrective genes that express modified human G6Pase-alpha proteins, directed by the tissue-specific human G6PC promoter/enhancer.
This technology can be independently licensed for development as a therapy. The NICHD inventor is also interested in the mechanisms by which GSD-1a may lead to hepatic malignancy and a collaboration project may be considered.
- Gene therapy vector for the delivery of a corrective gene to treat of GSD-Ia.
- Useful in development of a combined pharmaceutical plus gene therapy approach to treat adult GSD-1a patients at risk of hepatocellular carcinoma.
- Protein coding sequences are modified from the wildtype human sequence for enhanced enzymatic activity.
Lee YM et al. Prevention of hepatocellular adenoma and correction of metabolic abnormalities in murine
glycogen storage disease type Ia by gene therapy. Hepatology 2012 Nov;56(5):1719-29. 
Lee YM, et al. The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC
expression in murine glycogen storage disease type Ia. Mol Genet Metab. 2013 Nov;110(3):275-80. 
- U.S. Patent Filed: U.S. Patent Application Number 15/493,622, Filed 21 Apr 2017
- U.S. Patent Issued: U.S. Patent Number 10,113,183, Issued 30 Oct 2018