ArticlePloS one2010
Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- Therapeutic effects of lomerizine on vasculopathy in Fabry disease.Scientific reports · 2025Article
- Safety analysis of self-administered enzyme replacement therapy using data from the Fabry Outcome and Gaucher Outcome Surveys.Orphanet journal of rare diseases · 2025Observational
- Article
- Preclinical efficacy and safety of adeno-associated virus 5 alpha-galactosidase: A gene therapy for Fabry disease.Molecular therapy. Methods & clinical development · 2024Article
- Overcoming Resistance in Anderson-Fabry Disease: Current Therapeutic Challenges and Future Perspectives.Journal of clinical medicine · 2024Article
- Systematic gene therapy derived from an investigative study of AAV2/8 vector gene therapy for Fabry disease.Orphanet journal of rare diseases · 2023Article
- Fasudil alleviates the vascular endothelial dysfunction and several phenotypes of Fabry disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Anderson-Fabry disease cardiomyopathy: an update on epidemiology, diagnostic approach, management and monitoring strategies.Frontiers in cardiovascular medicine · 2023Review
- Endocrine disorders in patients with Fabry disease: insights from a reference centre prospective study.Endocrine · 2022Observational
- Substrate reduction therapy for Krabbe disease and metachromatic leukodystrophy using a novel ceramide galactosyltransferase inhibitor.Scientific reports · 2021Article
- Contemporary therapeutics and new drug developments for treatment of Fabry disease: a narrative review.Cardiovascular diagnosis and therapy · 2021Review
- New drugs for the treatment of Anderson-Fabry disease.Journal of nephrology · 2021Review
- Fabry disease: where are we now?International urology and nephrology · 2020Review
- Developments in the treatment of Fabry disease.Journal of inherited metabolic disease · 2020Review
- Lysosomal storage diseases: current therapies and future alternatives.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Article
- Glucosylceramide synthase inhibition with lucerastat lowers globotriaosylceramide and lysosome staining in cultured fibroblasts from Fabry patients with different mutation types.Human molecular genetics · 2018Article
- Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10.Scientific reports · 2018Article
- Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies.Disease models & mechanisms · 2017Review
- Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency in the activity of the lysosomal hydrolase α-galactosidase A (α-gal). This deficiency results in accumulation of the glycosphingolipid globotriaosylceramide (GL-3) in lysosomes. Endothelial cell storage of GL-3 frequently leads to kidney dysfunction, cardiac and cerebrovascular disease. The current treatment for Fabry disease is through infusions of recombinant α-gal (enzyme-replacement therapy; ERT). Although ERT can markedly reduce the lysosomal burden of GL-3 in endothelial cells, variability is seen in the clearance from several other cell types. This suggests that alternative and adjuvant therapies may be desirable. Use of glucosylceramide synthase inhibitors to abate the biosynthesis of glycosphingolipids (substrate reduction therapy, SRT) has been shown to be effective at reducing substrate levels in the related glycosphingolipidosis, Gaucher disease. Here, we show that such an inhibitor (eliglustat tartrate, Genz-112638) was effective at lowering GL-3 accumulation in a mouse model of Fabry disease. Relative efficacy of SRT and ERT at reducing GL-3 levels in Fabry mouse tissues differed with SRT being more effective in the kidney, and ERT more efficacious in the heart and liver. Combination therapy with ERT and SRT provided the most complete clearance of GL-3 from all the tissues. Furthermore, treatment normalized urine volume and uromodulin levels and significantly delayed the loss of a nociceptive response. The differential efficacies of SRT and ERT in the different tissues indicate that the combination approach is both additive and complementary suggesting the possibility of an improved therapeutic paradigm in the management of Fabry disease.
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