title: Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase.
abstract: OBJECTIVE
  Reversal of the hematologic and visceral abnormalities characteristic of Gaucher disease, the most common lipid storage disorder, with biweekly infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well documented. The extent to which the skeleton responds to enzyme replacement therapy has not been systematically investigated.
  
  
  METHODS
  To assess the skeletal response to enzyme replacement therapy, we treated 12 patients with type 1 Gaucher disease, who had intact spleens, with macrophage-targeted glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2 weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body weight every 2 weeks, each for 9 months.
  
  
  RESULTS
  The lipid composition of bone marrow, determined by direct chemical analysis, began to improve after 6 months of treatment at a time when noninvasive imaging studies showed no significant changes. By 42 months, improvement in marrow composition was demonstrable on all noninvasive, quantitative imaging modalities (magnetic resonance score, quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in this study. Quantitative chemical shift imaging, the most sensitive technique, demonstrated a dramatic normalization of the marrow fat content in all patients. Net increases in either cortical or trabecular bone mass, as assessed by combined cortical thickness measurements and dual-energy quantitative computed tomography, respectively, occurred in 10 patients.
  
  
  CONCLUSIONS
  Prolonged treatment over 3 1/2 years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked improvement occurs in marrow composition and bone mass in both children and adults.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: S H
authors.initials: SH
authors.lastname: Doppelt
authors.forename: H J
authors.initials: HJ
authors.lastname: Mankin
authors.forename: J M
authors.initials: JM
authors.lastname: Dambrosia
authors.forename: R J
authors.initials: RJ
authors.lastname: Xavier
authors.forename: K A
authors.initials: KA
authors.lastname: McKusick
authors.forename: B R
authors.initials: BR
authors.lastname: Rosen
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.forename: L T
authors.initials: LT
authors.lastname: Niklason
authors.forename: S C
authors.initials: SC
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density; D001853:Bone Marrow / Q000737:chemistry; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002648:Child; D016503:Drug Delivery Systems; D005260:Female; D005776:Gaucher Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000032:analysis; D008297:Male; D011877:Radionuclide Imaging
chemical_list: D008055:Lipids; D005962:Glucosylceramidase