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dc.contributor.authorDominique, Germain.
dc.contributor.authorDerralynn, Hughes.
dc.contributor.authorKathleen, Nicholls.
dc.contributor.authorDaniel, Bichet.
dc.contributor.authorGiugliani, Roberto.
dc.contributor.authorWilcox, William.
dc.contributor.authorAmartino, Hernán.
dc.contributor.authoret al.
dc.date.accessioned2019-11-11T18:09:31Z
dc.date.available2019-11-11T18:09:31Z
dc.date.issued2016-08-11
dc.identifier.citationN Engl J Med. 2016 Aug 11;375(6):545-55.en_US
dc.identifier.issn0028-4793
dc.identifier.urihttps://riu.austral.edu.ar/handle/123456789/756
dc.description.abstractBACKGROUND: 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.isoenen_US
dc.publisherMassachusetts Medical Societyen_US
dc.subjectEnfermedad de Fabryen_US
dc.subjectGalactosidasasen_US
dc.subjectPlacebosen_US
dc.titleTreatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.en_US
dc.typeArticleen_US


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