ArticleJournal of inherited metabolic disease2010
Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy.
Article in Journal of inherited metabolic disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Animal Models for the Study of Gaucher Disease.International journal of molecular sciences · 2023Review
- Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects,Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Allogeneic hematopoietic stem cell transplantation for treating severe lung involvement in Gaucher disease.Molecular genetics and metabolism reports · 2020Article
- Lysosomal storage diseases: current therapies and future alternatives.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Review
- Targeting Glucosylceramide Synthesis in the Treatment of Rare and Common Renal Disease.Seminars in nephrology · 2018Review
- Induced Pluripotent Stem Cell Modeling of Gaucher's Disease: What Have We Learned?International journal of molecular sciences · 2017Review
- Quantum dots and potential therapy for Krabbe's disease.Journal of neuroscience research · 2016Review
- Synthesis of a novel photoactivatable glucosylceramide cross-linker.Journal of lipid research · 2016Article
- Enhancement of human plasma glucosylceramide assay sensitivity using delipidized plasma.Molecular genetics and metabolism reports · 2016Article
- Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders.International journal of molecular sciences · 2016Review
- CNS-accessible Inhibitor of Glucosylceramide Synthase for Substrate Reduction Therapy of Neuronopathic Gaucher Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Combination Therapies for Lysosomal Storage Diseases: A Complex Answer to a Simple Problem.Pediatric endocrinology reviews : PER · 2016Review
- Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease.PloS one · 2016Article
- Eliglustat: A Review in Gaucher Disease Type 1.Drugs · 2015Review
- CNS, lung, and lymph node involvement in Gaucher disease type 3 after 11 years of therapy: clinical, histopathologic, and biochemical findings.Molecular genetics and metabolism · 2015Article
- Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease.Drug design, development and therapy · 2015Review
- The consequences of genetic and pharmacologic reduction in sphingolipid synthesis.Journal of inherited metabolic disease · 2015Review
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid beta-glucosidase), with consequent cellular accumulation of glucosylceramide (GL-1). The disease is managed by intravenous administrations of recombinant glucocerebrosidase (imiglucerase), although symptomatic patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy (ERT) is not an option may also be treated by substrate reduction therapy (SRT) with miglustat. To determine whether the sequential use of both ERT and SRT may provide additional benefits, we compared the relative pharmacodynamic efficacies of separate and sequential therapies in a murine model of Gaucher disease (D409V/null). As expected, ERT with recombinant glucocerebrosidase was effective in reducing the burden of GL-1 storage in the liver, spleen, and lung of 3-month-old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genz-112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genz-112638 showed the lowest levels of GL-1 in all the visceral organs and a reduced number of Gaucher cells in the liver. This was likely because the additional deployment of SRT following enzyme therapy slowed the rate of reaccumulation of GL-1 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genz-112638 could potentially be used as a convenient maintenance therapy. In patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.
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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.