title: Aerobic training as an adjunctive therapy to enzyme replacement in Pompe disease.
abstract: BACKGROUND
  Aerobic exercise may be used in conjunction with enzyme replacement therapy (ERT) to attenuate cardiovascular deconditioning, skeletal muscle wasting, and loss of motor function in Pompe disease (glycogen storage disease type II; GSDII), but the effects on lysosomal glycogen content and macroautophagy have not been defined to date.
  
  
  OBJECTIVE
  The main objectives of this study were to determine if acute aerobic exercise enhances 24-h uptake of recombinant human enzyme (rhGAA; Myozyme® [aim 1]) and if endurance training improves disease pathology when combined with ERT [aim 2] in Pompe mice.
  
  
  METHODS
  For the first aim in our study, Pompe mutant mice (6(neo)/6(neo)) were grouped into ERT (Myozyme® injection only [40 mg/kg]) and ERT+EX (Myozyme® injection followed by 90 min treadmill exercise) cohorts, and enzyme uptake was assessed in the heart and quadriceps 24h post injection. For the second aim of our study, mutant mice were randomized into control, endurance-trained, enzyme-treated, or combination therapy groups. Exercised animals underwent 14 weeks of progressive treadmill training with or without biweekly Myozyme® injections (40 mg/kg) and tissues were harvested 1 week post last treatment.
  
  
  RESULTS
  Myozyme® uptake (GAA activity) was not improved in ERT+EX over ERT alone at 24-h post injection. Endurance exercise training, with or without ERT, improved aerobic capacity and normalized grip strength, motor function, and lean mass (P<0.05), but did not reduce glycogen content or normalize macroautophagy beyond traditional enzyme replacement therapy.
  
  
  CONCLUSIONS
  Endurance training is beneficial as an adjunctive therapy to ERT in Pompe disease, although it works by mechanisms independent of a reduction in glycogen content.
authors.affiliation: Department of Pediatrics and Medicine, Neuromuscular Clinic, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mats I
authors.initials: MI
authors.lastname: Nilsson
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Samjoo
authors.forename: Bart P
authors.initials: BP
authors.lastname: Hettinga
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Koeberl
authors.forename: Haoyue
authors.initials: H
authors.lastname: Zhang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hawke
authors.forename: Aliyah A
authors.initials: AA
authors.lastname: Nissar
authors.forename: Tahir
authors.initials: T
authors.lastname: Ali
authors.forename: Linda
authors.initials: L
authors.lastname: Brandt
authors.forename: Mohammad U
authors.initials: MU
authors.lastname: Ansari
authors.forename: Hassan
authors.initials: H
authors.lastname: Hazari
authors.forename: Neha
authors.initials: N
authors.lastname: Patel
authors.forename: Jaihoon
authors.initials: J
authors.lastname: Amon
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D000818:Animals; D056947:Enzyme Replacement Therapy; D015444:Exercise; D005081:Exercise Therapy; D005260:Female; D006003:Glycogen / Q000378:metabolism*; D006009:Glycogen Storage Disease Type II / Q000201:enzymology* / Q000473:pathology / Q000628:therapy*; D006321:Heart / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010805:Physical Conditioning, Animal; D000520:alpha-Glucosidases / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D006003:Glycogen; C509951:GAA protein, human; D000520:alpha-Glucosidases