Correction of Disease Phenotype in Pompe Disease Knockout Mice Following Cationic Lipid-GL-67-Mediated Gene Therapy

Background: Genetic deficiency of lysosomal acid α-glucosidase or acid maltase (GAA) results in Pompe disease (PD) or glycogen storage disease type II, encompassing subtypes of varying severity. The infantile form presents as hypotonia, muscle weakness, and congestive heart failure in the first year, while the adult onset forms are limited to skeletal muscle. Gene therapy for diseases that affect muscles or organs (as PD) may be very difficult due to their size or location and our ability to transfect these organs with high efficiency. Methods: cDNA complexed with the cationic lipid GL-67 as a delivery system for therapy of PD. Results: expression plasmid. Cells showed a significant increase in human GAA activity with 20 nmol of the cationic lipid, resulting in maximal expression. GAA knockout mice were treated intraperitoneally every 2 weeks for four months with 100 µg of plasmid and 2 mM GL-67 lipid. Tissues, including heart, diaphragm, and skeletal muscle showed substantial increase in GAA activity. More important, the clinical phenotype of hind and forelimb muscle weakness was reversed and life span extended to almost normal longevity. Conclusions: cDNA may be an effective treatment for PD.