title: Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.
abstract: OBJECTIVE
  To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease.
  
  
  METHODS
  We enrolled 8 infant patients who had Pompe disease with GAA activity <1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks. Safety measurements included adverse events, laboratory tests, and anti-rhGAA antibody titers. Efficacy evaluations included survival, ventilator use, echocardiograms, growth, and motor and cognitive function.
  
  
  RESULTS
  After 52 weeks of treatment, 6 of 8 patients were alive, and 5 patients were free of invasive ventilator support. Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition. Five patients acquired new motor milestones; 3 patients walked independently. Four patients died after the initial study phase; the median age at death or treatment withdrawal for all patients was 21.7 months, significantly later than expected for patients who were not treated. Treatment was safe and well tolerated; no death was drug-related.
  
  
  CONCLUSIONS
  rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA. kishn001@mc.duke.edu
authors.forename: Priya Sunil
authors.initials: PS
authors.lastname: Kishnani
authors.forename: Marc
authors.initials: M
authors.lastname: Nicolino
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Rogers
authors.forename: Anne Chun-Hui
authors.initials: AC
authors.lastname: Tsai
authors.forename: John
authors.initials: J
authors.lastname: Waterson
authors.forename: Gail E
authors.initials: GE
authors.lastname: Herman
authors.forename: Andreas
authors.initials: A
authors.lastname: Amalfitano
authors.forename: Beth L
authors.initials: BL
authors.lastname: Thurberg
authors.forename: Susan
authors.initials: S
authors.lastname: Richards
authors.forename: Mark
authors.initials: M
authors.lastname: Davison
authors.forename: Deyanira
authors.initials: D
authors.lastname: Corzo
authors.forename: Y T
authors.initials: YT
authors.lastname: Chen
mesh_terms: D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy / Q000209:etiology; D002657:Child Development; D005060:Europe / Q000453:epidemiology; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D006311:Hearing Disorders / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D009123:Muscle Hypotonia / Q000188:drug therapy / Q000209:etiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D012121:Respiration, Artificial; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D000520:alpha-Glucosidases / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D006003:Glycogen; C509951:GAA protein, human; D000520:alpha-Glucosidases