ArticleMolecular medicine (Cambridge, Mass.)2015
Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 99 citations in OpenAlex.
- Historical Control Analysis Demonstrates Greater Long-Term Reduction in Plasma Globotriaosylceramide (Gb3) by Venglustat Compared With Placebo or Agalsidase Beta in Male Patients With Classic Fabry Disease.Molecular genetics & genomic medicine · 2025Trial
- Venglustat, an orally administered glucosylceramide synthase inhibitor: Assessment over 3 years in adult males with classic Fabry disease in an open-label phase 2 study and its extension study.Molecular genetics and metabolism · 2023Trial
- Assessment of Target Engagement in a First-in-Human Trial with Sinbaglustat, an Iminosugar to Treat Lysosomal Storage Disorders.Clinical and translational science · 2021Trial
- Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral Venglustat in Healthy Volunteers.Clinical pharmacology in drug development · 2021Trial
- Clinical manifestations, diagnosis, and management of renal involvement in Fabry disease.Renal failure · 2026Review
- Fabry Disease: An Updated Perspective and Review of Treatment and Therapies.Advances in therapy · 2026Review
- Liver Gene Therapy in Fabry Disease Mice With Low Doses of rAAV2/8 Expressing a Codon-Optimized hGLA cDNA Results in Long-Term Disease Correction.Journal of inherited metabolic disease · 2026Article
- Metabolic rerouting of valine and isoleucine oxidation increases survival in zebrafish models of disorders of propionyl-CoA metabolism.Human molecular genetics · 2025Article
- Cardiac manifestations of Fabry disease.NPJ cardiovascular health · 2025Review
- Progress and Challenges in the Treatment of Fabry Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Selective requirement of glycosphingolipid synthesis for natural killer and cytotoxic T cells.Cell · 2025Article
- Article
- Therapeutic landscape of Fabry disease: advances and challenges from classical strategies to emerging therapies.Frontiers in medicine · 2025Review
- Article
- Preclinical efficacy and safety of adeno-associated virus 5 alpha-galactosidase: A gene therapy for Fabry disease.Molecular therapy. Methods & clinical development · 2024Article
- [What is confirmed in the treatment of Fabry's disease?]Innere Medizin (Heidelberg, Germany) · 2024Review
- Overcoming Resistance in Anderson-Fabry Disease: Current Therapeutic Challenges and Future Perspectives.Journal of clinical medicine · 2024Article
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- Emerging role of MAPK signaling in glycosphingolipid-associated tumorigenesis.Glycoconjugate journal · 2024Review
- Hypertrophic Cardiomyopathy versus Storage Diseases with Myocardial Involvement.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fabry disease, an X-linked glycosphingolipid storage disorder, is caused by the deficient activity of α-galactosidase A (α-Gal A). This results in the lysosomal accumulation in various cell types of its glycolipid substrates, including globotriaosylceramide (GL-3) and lysoglobotriaosylceramide (globotriaosyl lysosphingolipid, lyso-GL-3), leading to kidney, heart, and cerebrovascular disease. To complement and potentially augment the current standard of care, biweekly infusions of recombinant α-Gal A, the merits of substrate reduction therapy (SRT) by selectively inhibiting glucosylceramide synthase (GCS) were examined. Here, we report the development of a novel, orally available GCS inhibitor (Genz-682452) with pharmacological and safety profiles that have potential for treating Fabry disease. Treating Fabry mice with Genz-682452 resulted in reduced tissue levels of GL-3 and lyso-GL-3 and a delayed loss of the thermal nociceptive response. Greatest improvements were realized when the therapeutic intervention was administered to younger mice before they developed overt pathology. Importantly, as the pharmacologic profiles of α-Gal A and Genz-682452 are different, treating animals with both drugs conferred the greatest efficacy. For example, because Genz-682452, but not α-Gal A, can traverse the blood-brain barrier, levels of accumulated glycosphingolipids were reduced in the brain of Genz-682452-treated but not α-Gal A-treated mice. These results suggest that combining substrate reduction and enzyme replacement may confer both complementary and additive therapeutic benefits in Fabry disease.
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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.