Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II

Pompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency o f acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and smooth muscle. There is currently no treatm ent for this fatal disease, but the applicability of enzyme replacement the rapy is under investigation. For this purpose, recombinant human acid alpha -glucosidase has been produced on an industrial scale in the milk of transg enic rabbits. In this paper we demonstrate the therapeutic effect of this e nzyme in our knockout mouse model of GSDII. Full correction of acid alpha-g lucosidase deficiency was obtained in all tissues except brain after a sing le dose of i.v. enzyme administration. Weekly enzyme infusions over a perio d of 6 months resulted in degradation of lysosomal glycogen in heart, skele tal and smooth muscle. The tissue morphology improved substantially despite the advanced state of disease at the start of treatment, The results have led to the start of a Phase II clinical trial of enzyme replacement therapy in patients.