Pre-clinical (in vivo)
- 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.
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 Developmentdeveloped 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.
- Protein coding sequences are modified from the wildtype human sequence for enhanced enzymatic activity.