title: Enzyme replacement therapy in late-onset Pompe's disease: a three-year follow-up.
abstract: Pompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen is caused by acid alpha-glucosidase deficiency. Patients with late-onset Pompe's disease present with progressive muscle weakness also affecting pulmonary function. In search of a treatment, we investigated the feasibility of enzyme replacement therapy with recombinant human alpha-glucosidase from rabbit milk. Three patients (aged 11, 16, and 32 years) were enrolled in the study. They were all wheelchair-bound and two of them were ventilator dependent with a history of deteriorating pulmonary function. After 3 years of treatment with weekly infusions of alpha-glucosidase, the patients had stabilized pulmonary function and reported less fatigue. The youngest and least affected patient showed an impressive improvement of skeletal muscle strength and function. After 72 weeks of treatment, he could walk without support and finally abandoned his wheelchair. Our findings demonstrate that recombinant human alpha-glucosidase from rabbit milk has a therapeutic effect in late-onset Pompe's disease. There is good reason to continue the development of enzyme replacement therapy for Pompe's disease and to explore further the production of human therapeutic proteins in the milk of mammals.
authors.affiliation: Department of Pediatrics, Division of Metabolic Diseases and Genetics, Erasmus MC-Sophia, Rotterdam, The Netherlands.
authors.forename: Léon P F
authors.initials: LP
authors.lastname: Winkel
authors.forename: Johanna M P
authors.initials: JM
authors.lastname: Van den Hout
authors.forename: Joep H J
authors.initials: JH
authors.lastname: Kamphoven
authors.forename: Janus A M
authors.initials: JA
authors.lastname: Disseldorp
authors.forename: Maaike
authors.initials: M
authors.lastname: Remmerswaal
authors.forename: Willem F M
authors.initials: WF
authors.lastname: Arts
authors.forename: M Christa B
authors.initials: MC
authors.lastname: Loonen
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Vulto
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Van Doorn
authors.forename: Gerard
authors.initials: G
authors.lastname: De Jong
authors.forename: Wim
authors.initials: W
authors.lastname: Hop
authors.forename: G Peter A
authors.initials: GP
authors.lastname: Smit
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Shapira
authors.forename: Marijke A
authors.initials: MA
authors.lastname: Boer
authors.forename: Otto P
authors.initials: OP
authors.lastname: van Diggelen
authors.forename: Arnold J J
authors.initials: AJ
authors.lastname: Reuser
authors.forename: Ans T
authors.initials: AT
authors.lastname: Van der Ploeg
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D016014:Linear Models; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010865:Pilot Projects; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D000520:alpha-Glucosidases / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D000520:alpha-Glucosidases