title: Evaluation of a low dose, after a standard therapeutic dose, of agalsidase beta during enzyme replacement therapy in patients with Fabry disease.
abstract: OBJECTIVE
  Fabry disease, a genetic deficiency of alpha-galactosidase A, is characterized by pathogenic cellular accumulation of globotriaosylceramide. During clinical trials, recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme, Genzyme Corporation, Cambridge, MA), infused intravenously at 1.0 mg/kg every 2 weeks for 6 months, cleared or reduced globotriaosylceramide in renal, cardiac, and dermal microvascular endothelia and other cells, with results sustained for up to 5 years in most patients evaluated. This study explored whether a lower dose could maintain globotriaosylceramide clearance achieved with 1.0 mg/kg.
  
  
  METHODS
  Cellular globotriaosylceramide levels were assessed histologically in kidney and skin biopsies from 21 adult Fabry males treated for 6 months at 1.0 mg/kg/2 weeks followed by 18 months at 0.3 mg/kg/2 weeks.
  
  
  RESULTS
  In kidney interstitial capillary endothelium, the primary endpoint, globotriaosylceramide clearance was achieved in 100% of patients with 1.0 mg/kg and maintained in 90% with 0.3 mg/kg. In seven other renal cell types and superficial dermal capillary endothelium, globotriaosylceramide reduction or clearance was maintained with 0.3 mg/kg in approximately 70% of patients.
  
  
  CONCLUSIONS
  A lower dose of agalsidase beta may be sufficient in some, but not all, patients with Fabry disease to maintain the cellular globotriaosylceramide clearance achieved with 1.0 mg/kg/2 weeks. Long-term clinical effects of transitioning to the lower dose have not been evaluated.
authors.affiliation: Clinical Department of Cardiology and Angiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic. lubanda@mail.cz
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lubanda
authors.forename: Ene
authors.initials: E
authors.lastname: Anijalg
authors.forename: Vladimír
authors.initials: V
authors.lastname: Bzdúch
authors.forename: Beth L
authors.initials: BL
authors.lastname: Thurberg
authors.forename: Bernard
authors.initials: B
authors.lastname: Bénichou
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymanska
mesh_terms: D000328:Adult; D001706:Biopsy; D023341:Chills / Q000139:chemically induced; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D000795:Fabry Disease / Q000188:drug therapy* / Q000473:pathology; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014281:Trihexosylceramides / Q000097:blood / Q000378:metabolism / Q000652:urine; D055815:Young Adult; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase; C459420:agalsidase beta