Trial reportOrphanet journal of rare diseases2012
Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies.
Trial report in Orphanet journal of rare diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2, Open-Label, Single Dose Level, 24-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
A Phase 2, Open-Label, Single Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Who cites it
38 citing papers in PubMed, 102 citations in OpenAlex.
- Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Trial
- Trial
- Modeling Fabry nephropathy: insights from experimental systems towards precision nephrology.Disease models & mechanisms · 2026Review
- Therapeutic effects of lomerizine on vasculopathy in Fabry disease.Scientific reports · 2025Article
- Impact of kidney biopsy on deciding when to initiate enzyme replacement therapy in children with Fabry disease.Pediatric nephrology (Berlin, Germany) · 2024Article
- Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes.Journal of medical genetics · 2023Article
- Imaging of metabolic and overload disorders in tissues and organs.Japanese journal of radiology · 2023Review
- Fasudil alleviates the vascular endothelial dysfunction and several phenotypes of Fabry disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Drug screening identifies tazarotene and bexarotene as therapeutic agents in multiple sulfatase deficiency.EMBO molecular medicine · 2023Article
- Renal Manifestations of Fabry Disease: A Narrative Review.Canadian journal of kidney health and disease · 2021Review
- Review
- The GALA project: practical recommendations for the use of migalastat in clinical practice on the basis of a structured survey among Italian experts.Orphanet journal of rare diseases · 2020Article
- Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients.Clinical genetics · 2019Article
- Oral Chaperone Therapy Migalastat for Treating Fabry Disease: Enzymatic Response and Serum Biomarker Changes After 1 Year.Clinical pharmacology and therapeutics · 2019Article
- Migalastat: A Review in Fabry Disease.Drugs · 2019Review
- Glycoside Mimics from Glycosylamines: Recent Progress.Molecules (Basel, Switzerland) · 2018Review
- In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease.Journal of visualized experiments : JoVE · 2017Article
- Enzyme replacement therapy and beyond-in memoriam Roscoe O. Brady, M.D. (1923-2016).Journal of inherited metabolic disease · 2017Review
- The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat.Genetics in medicine : official journal of the American College of Medical Genetics · 2017Article
- Small molecules as therapeutic agents for inborn errors of metabolism.Journal of inherited metabolic disease · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundFabry disease (FD) is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A), which leads to globotriaosylceramide (GL-3) accumulation in multiple tissues. We report on the safety and pharmacodynamics of migalastat hydrochloride, an investigational pharmacological chaperone given orally at 150 mg every-other-day.
methodsTwo open-label uncontrolled phase 2 studies of 12 and 24 weeks (NCT00283959 and NCT00283933) in 9 males with FD were combined. At multiple time points, α-Gal A activity and GL-3 levels were quantified in blood cells, kidney and skin. GL-3 levels were also evaluated through skin and renal histology.
resultsCompared to baseline, increased α-Gal A activity of at least 50% was demonstrated in blood, skin and kidney in 6 of 9 patients. Patients' increased α-Gal A activities paralleled the α-Gal A increases observed in vitro in HEK-293 cells transfected with the corresponding mutant form of the enzyme. The same 6 patients who demonstrated increases of α-Gal A activity also had GL-3 reduction in skin, urine and/or kidney, and had α-Gal A mutations that responded in transfected cells incubated with the drug. The 3 patients who did not show a consistent response in vivo had α-Gal A mutations that did not respond to migalastat HCl in transfected cells. Migalastat HCl was well tolerated.
conclusionsMigalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD. It enhanced α-Gal A activity and resulted in GL-3 substrate decrease in patients with responsive GLA mutations. Phase 3 studies are ongoing.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.