Secretion of Native Recombinant Lysosomal Enzymes by Liver
Description of Invention:
Glycogen storage disease type II (GSDII) is an autosomal recessive disorder caused by the deficiency of acid alpha-glucosidase (GAA), a glycogen-degrading lysosomal enzyme. This deficiency results in generalized deposition of lysosomal glycogen in almost all tissues of the body and can ultimately lead to cardiac failure before the age of two years. Current treatment for the disease includes repairing the deficiency by injecting recombinant protein into the patient made from either cultured Chinese Hamster Ovary (CHO) cells or secreted in the milk from rabbits that bear the transgene for the protein under a milk-specific promoter. Both recombinant proteins produced are extremely inefficient in their uptake into and function in targeted tissues.
The NIH announces a new technology that relates to the use of hepatocytes whether in culture or in vivo for the production of human GAA. The hepatocytes produce appropriate post-translational modification of the enzyme in liver cells by proper glycosylation, thereby producing a superior enzyme capable of being easily taken up and localized intracellularly in the target tissue. Once there, the enzyme digests glycogen present in lysosomes.
For Additional Information Please Contact: Tara L. Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4426
Email: tarak@mail.nih.gov
Fax: (301)402-0220
