Kamath, Ravi S.Lukina, ElenaWatman, NoraDragosky, MartaPastores, Gregory M.Arreguin, Elsa AvilaRosenbaum, HannaZimran, AriAguzzi, RashaPuga, Ana CristinaNorfleet, Andrea M.Peterschmitt, M. JudithRosenthal, Daniel2014-09-082014Kamath, R. S., E. Lukina, N. Watman, M. Dragosky, G. M. Pastores, E. A. Arreguin, H. Rosenbaum, et al. 2014. “Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat.” Skeletal Radiology 43 (10): 1353-1360. doi:10.1007/s00256-014-1891-9. http://dx.doi.org/10.1007/s00256-014-1891-9.0364-2348http://nrs.harvard.edu/urn-3:HUL.InstRepos:12785913Objective: 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). Materials and 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.en-USGaucher disease type 1Bone diseaseDrug therapyTargeted molecular therapyMagnetic resonance imagingDual-energy X-ray absorptiometryJournal Article2014-09-0810.1007/s00256-014-1891-9