title: Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial.
abstract: Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy. We report on the results of a phase II clinical trial including two patients with classical infantile Pompe disease receiving enzyme replacement therapy over a period of 48 weeks by weekly infusions. Recombinant acid alpha-glucosidase was derived from the milk of transgenic rabbits. Safety was evaluated by recording adverse events while clinical efficacy was evaluated by ventilator-free survival, left ventricular mass index, motor development as well as histologic and biochemical analysis of muscle biopsies. This therapy was in general well-tolerated. There was an overall improvement in left ventricular mass, cardiac function, skeletal muscle function and histological appearance of skeletal muscle.
authors.affiliation: Department of Paediatrics and Paediatric Neurology, University of Essen, Hufelandstrasse 55, 45 122 Essen, Germany. lars.klinge@uni-essen.de
authors.forename: L
authors.initials: L
authors.lastname: Klinge
authors.forename: V
authors.initials: V
authors.lastname: Straub
authors.forename: U
authors.initials: U
authors.lastname: Neudorf
authors.forename: J
authors.initials: J
authors.lastname: Schaper
authors.forename: T
authors.initials: T
authors.lastname: Bosbach
authors.forename: K
authors.initials: K
authors.lastname: Görlinger
authors.forename: M
authors.initials: M
authors.lastname: Wallot
authors.forename: S
authors.initials: S
authors.lastname: Richards
authors.forename: T
authors.initials: T
authors.lastname: Voit
mesh_terms: D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D006003:Glycogen; D000520:alpha-Glucosidases