Improved Gene Therapy Vectors for the Treatment of Glycogen Storage Disease Type Ia (GSD-1a)

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.