Anaphylaxis and Immune Toxicities Are Dose Dependent Following ERT with Recombinant Alpha Glucosidase and Affected by Type of Mutation in Pompe Disease

Pompe disease is a lysosomal storage deficiency caused by mutations to the acid alpha glucosidase (GAA) gene. Early onset patients are characterized by severe cardiomegaly, respiratory distress and muscle weakness, resulting in mortality within a year of birth without treatment. Recombinant human acid alpha glucosidase (rhGAA) enzyme replacement therapy (ERT) is the current standard of care; however, these patients develop severe immune responses to the therapy that reduces the efficiency of treatment. Immune responses include infusion associated reactions (IAR) and high anti-rhGAA titer that further limits efficiency and can alter the course of treatment. The data support the hypothesis that reducing the dose of ERT required for therapeutic intervention (possibly by increasing the efficiency of lysosomal uptake of rhGAA or the use of stabilizing chaperones) will reduce the rhGAA associated immune responses and toxicities in ERT for Pompe disease.