Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.

DSpace/Manakin Repository

Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.

Show simple item record

dc.contributor.author Dominique, Germain.
dc.contributor.author Derralynn, Hughes.
dc.contributor.author Kathleen, Nicholls.
dc.contributor.author Daniel, Bichet.
dc.contributor.author Giugliani, Roberto.
dc.contributor.author Wilcox, William.
dc.contributor.author Amartino, Hernan.
dc.contributor.author et al.
dc.date.accessioned 2019-11-11T18:09:31Z
dc.date.available 2019-11-11T18:09:31Z
dc.date.issued 2016-08-11
dc.identifier.citation N Engl J Med. 2016 Aug 11;375(6):545-55. en_US
dc.identifier.issn 0028-4793
dc.identifier.uri https://riu.austral.edu.ar/handle/123456789/756
dc.description.abstract BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes. METHODS: The initial assay of mutant α-galactosidase forms that we used to categorize 67 patients with Fabry's disease for randomization to 6 months of double-blind migalastat or placebo (stage 1), followed by open-label migalastat from 6 to 12 months (stage 2) plus an additional year, had certain limitations. Before unblinding, a new, validated assay showed that 50 of the 67 participants had mutant α-galactosidase forms suitable for targeting by migalastat. The primary end point was the percentage of patients who had a response (≥50% reduction in the number of globotriaosylceramide inclusions per kidney interstitial capillary) at 6 months. We assessed safety along with disease substrates and renal, cardiovascular, and patient-reported outcomes. RESULTS: The primary end-point analysis, involving patients with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy, did not show a significant treatment effect: 13 of 32 patients (41%) who received migalastat and 9 of 32 patients (28%) who received placebo had a response at 6 months (P=0.30). Among patients with suitable mutant α-galactosidase who received migalastat for up to 24 months, the annualized changes from baseline in the estimated glomerular filtration rate (GFR) and measured GFR were -0.30±0.66 and -1.51±1.33 ml per minute per 1.73 m(2) of body-surface area, respectively. The left-ventricular-mass index decreased significantly from baseline (-7.7 g per square meter; 95% confidence interval [CI], -15.4 to -0.01), particularly when left ventricular hypertrophy was present (-18.6 g per square meter; 95% CI, -38.2 to 1.0). The severity of diarrhea, reflux, and indigestion decreased. CONCLUSIONS: Among all randomly assigned patients (with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy), the percentage of patients who had a response at 6 months did not differ significantly between the migalastat group and the placebo group. (Funded by Amicus Therapeutics; ClinicalTrials.gov numbers, NCT00925301 [study AT1001-011] and NCT01458119 [study AT1001-041].). en_US
dc.language.iso en en_US
dc.publisher Massachusetts Medical Society en_US
dc.subject Enfermedad de Fabry en_US
dc.subject Galactosidasas en_US
dc.subject Placebos en_US
dc.title Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. en_US
dc.type Article en_US


Files in this item

Files Size Format View Description
N Engl J Med. 2016 Aug 11;375(6);545-55..pdf 178.8Kb PDF View/Open IA - Dominique

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account