ArticleHuman molecular genetics2018
Glucosylceramide synthase inhibition with lucerastat lowers globotriaosylceramide and lysosome staining in cultured fibroblasts from Fabry patients with different mutation types.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- Population Pharmacokinetic Modeling for the Iminosugar Lucerastat Supports Dose Adaptation in Patients With Fabry Disease and Moderate to Severe Renal Function Impairment.Journal of clinical pharmacology · 2026Trial
- Lucerastat, an oral therapy for Fabry disease: results from a pivotal randomized phase 3 study and its open-label extension.Nature communications · 2026Trial
- The effect of the glucosylceramide synthase inhibitor lucerastat on cardiac repolarization: results from a thorough QT study in healthy subjects.Orphanet journal of rare diseases · 2020Trial
- Fabry Disease: An Updated Perspective and Review of Treatment and Therapies.Advances in therapy · 2026Review
- Sinbaglustat is efficacious in GM2 gangliosidosis primarily through inhibition of GBA2 rather than GCS.Molecular therapy. Advances · 2026Article
- A new approach methodology for studying intrinsic ventricular arrhythmias in Fabry disease.Frontiers in cardiovascular medicine · 2026Article
- GLA is associated with ESCC progression and chemotherapy response via DNA damage repair-related pathways.Frontiers in oncology · 2026Article
- Lectin-Based Substrate Detection in Fabry Disease Using the Gb3-Binding Lectins StxB and LecA.International journal of molecular sciences · 2025Article
- Human in vitro models for Fabry disease: new paths for unravelling disease mechanisms and therapies.Journal of translational medicine · 2024Review
- Review
- Pharmacokinetics, Safety, and Tolerability of Single-Dose Orally Administered Venglustat in Healthy Chinese Volunteers.Clinical drug investigation · 2023Article
- Fabry Disease: Current and Novel Therapeutic Strategies. A Narrative Review.Current neuropharmacology · 2023Review
- Cardiovascular Involvement in Fabry's Disease: New Advances in Diagnostic Strategies, Outcome Prediction and Management.Cardiac failure review · 2023Review
- Dysregulated DNA methylation in the pathogenesis of Fabry disease.Molecular genetics and metabolism reports · 2022Article
- Glucosylceramide synthase inhibition protects against cardiac hypertrophy in chronic kidney disease.Scientific reports · 2022Article
- Understanding and modifying Fabry disease: Rationale and design of a pivotal Phase 3 study and results from a patient-reported outcome validation study.Molecular genetics and metabolism reports · 2022Article
- Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease.Journal of nanobiotechnology · 2022Article
- Expert opinion on the recognition, diagnosis and management of children and adults with Fabry disease: a multidisciplinary Turkey perspective.Orphanet journal of rare diseases · 2022Review
- Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype.EMBO molecular medicine · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene coding for α-galactosidase A (α-GalA). The deleterious mutations lead to accumulation of α-GalA substrates, including globotriaosylceramide (Gb3) and globotriaosylsphingosine. Progressive glycolipid storage results in cellular dysfunction, leading to organ damage and clinical disease, i.e. neuropathic pain, impaired renal function and cardiomyopathy. Many Fabry patients are treated by bi-weekly intravenous infusions of replacement enzyme. While the only available oral therapy is an α-GalA chaperone, which is indicated for a limited number of patients with specific 'amenable' mutations. Lucerastat is an orally bioavailable inhibitor of glucosylceramide synthase (GCS) that is in late stage clinical development for Fabry disease. Here we investigated the ability of lucerastat to lower Gb3, globotriaosylsphingosine and lysosomal staining in cultured fibroblasts from 15 different Fabry patients. Patients' cells included 13 different pathogenic variants, with 13 cell lines harboring GLA mutations associated with the classic disease phenotype. Lucerastat dose dependently reduced Gb3 in all cell lines. For 13 cell lines the Gb3 data could be fit to an IC50 curve, giving a median IC50 [interquartile range (IQR)] = 11 μM (8.2-18); the median percent reduction (IQR) in Gb3 was 77% (70-83). Lucerastat treatment also dose dependently reduced LysoTracker Red staining of acidic compartments. Lucerastat's effects in the cell lines were compared to those with current treatments-agalsidase alfa and migalastat. Consequently, the GCS inhibitor lucerastat provides a viable mechanism to reduce Gb3 accumulation and lysosome volume, suitable for all Fabry patients regardless of genotype.
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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.