title: Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II.
abstract: Pompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and smooth muscle. There is currently no treatment for this fatal disease, but the applicability of enzyme replacement therapy is under investigation. For this purpose, recombinant human acid alpha-glucosidase has been produced on an industrial scale in the milk of transgenic rabbits. In this paper we demonstrate the therapeutic effect of this enzyme in our knockout mouse model of GSDII. Full correction of acid alpha-glucosidase deficiency was obtained in all tissues except brain after a single dose of i.v. enzyme administration. Weekly enzyme infusions over a period of 6 months resulted in degradation of lysosomal glycogen in heart, skeletal 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.
authors.affiliation: Department of Clinical Genetics,Erasmus University Rotterdam and Sophia Children's Hospital, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Bijvoet
authors.forename: H
authors.initials: H
authors.lastname: Van Hirtum
authors.forename: M A
authors.initials: MA
authors.lastname: Kroos
authors.forename: E H
authors.initials: EH
authors.lastname: Van de Kamp
authors.forename: O
authors.initials: O
authors.lastname: Schoneveld
authors.forename: P
authors.initials: P
authors.lastname: Visser
authors.forename: J P
authors.initials: JP
authors.lastname: Brakenhoff
authors.forename: M
authors.initials: M
authors.lastname: Weggeman
authors.forename: E J
authors.initials: EJ
authors.lastname: van Corven
authors.forename: A T
authors.initials: AT
authors.lastname: Van der Ploeg
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005087:Glucan 1,4-alpha-Glucosidase / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008892:Milk / Q000201:enzymology*; D009206:Myocardium / Q000648:ultrastructure; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D000520:alpha-Glucosidases
chemical_list: D011994:Recombinant Proteins; D000520:alpha-Glucosidases; D005087:Glucan 1,4-alpha-Glucosidase