Dr. A. Amalfitano DO, PhD
Duke University Medical Centre
United States of America
Enzyme Replacement Therapy
Glycogen Storage Disease Type II (GSD-II) is an autosomal recessive disorder that results in a lack of adequate production of the acid-alpha-glucosidase enzyme (GAA) in the skeletal and cardiac muscles of affected individuals. Our group is investigating a variety of methods to potentially treat this disorder, focusing both upon enzyme replacement and gene therapy strategies. For example, intravenous administration of the human GAA enzyme (produced via recombinant cell lines) resulted in a rapid correction of the muscle pathology noted in an animal model of GSD-II, the acid-maltase deficient quail. Based upon these promising results, we have recently initiated a Phase I/II clinical trial investigating the potential of recombinant human GAA to safely treat individuals affected by GSD-II.
Since GSD-II is a genetic disorder, we are also investigating the potential of gene therapy strategies for the treatment of GSD-II. Recently, our group uniquely demonstrated that a simple intravenous administration of an Adenovirus vector encoding GAA resulted in hepatic transduction and high level secretion of the GAA enzyme into the bloodstream of GSD-II knockout mice. The circulatory system then distributed the GAA enzyme to affected muscle groups, resulting in a systemic reduction of glycogen accumulation in the respective muscles. Together, our studies suggest that a variety of treatment strategies may have potential for use in the treatment of individuals affected by GSD-II.