title: Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat.
abstract: OBJECTIVE
  Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150).
  
  
  METHODS
  Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year.
  
  
  RESULTS
  Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9% (14.2%) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56%) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42%) patients had focal bone lesions, which remained stable, and 7/19 (37%) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved.
  
  
  CONCLUSIONS
  Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kamath
authors.forename: Elena
authors.initials: E
authors.lastname: Lukina
authors.forename: Nora
authors.initials: N
authors.lastname: Watman
authors.forename: Marta
authors.initials: M
authors.lastname: Dragosky
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
authors.forename: Elsa Avila
authors.initials: EA
authors.lastname: Arreguin
authors.forename: Hanna
authors.initials: H
authors.lastname: Rosenbaum
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
authors.forename: Rasha
authors.initials: R
authors.lastname: Aguzzi
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Puga
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Norfleet
authors.forename: M Judith
authors.initials: MJ
authors.lastname: Peterschmitt
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Rosenthal
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018488:Bone Demineralization, Pathologic / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D015519:Bone Density / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control; D005776:Gaucher Disease / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011759:Pyrrolidines / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; C522917:eliglustat