The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: A position statement

@article{Cox2004TheRO,
  title={The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: A position statement},
  author={Timothy Martin Cox and Johannes Aerts and Generoso Andria and Michael Beck and Nadia Belmatoug and Bruno Bembi and Raul Chertkoff and Stephan vom Dahl and Deborah Elstein and Anders Erikson and Manuel Giralt and Rene Heitner and Carla E. M. Hollak and Martin Hřeb{\'i}{\vc}ek and S. Lewis and Atual Mehta and Gregory M. Pastores and Arndt Rolfs and Maria Clara S{\'a} Miranda and Ari Zimran},
  journal={Journal of Inherited Metabolic Disease},
  year={2004},
  volume={26},
  pages={513-526}
}
N-Butyldeoxynojirimycin (NB-DNJ, miglustat 'Zavesca') is an orallyactive iminosugar which inhibits the biosynthesis of macromolecular substrates that accumulate pathologically in glycosphingolipidoses. Clinical trials of NB-DNJ in patients with Gaucher's disease demonstrate the therapeutic potential of such substrate inhibitors in the glycolipid storage disorders. However, macrophage-targetted enzyme replacement using intravenous mannose-terminated human glucocerebrosidase (imiglucerase… 
Design and synthesis of iminosugar-based inhibitors of glucosylceramide synthase: the search for new therapeutic agents against Gaucher disease
Abstract A series of iminosugars bearing two or three alkyl chains (‘iminoglycolipids’) were designed as ceramide mimics and analogues of N -butyl 1-deoxynojirimycin ( N -Bu DNJ, Zavesca ® ). This
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TLDR
Treatment of Sandhoff mice with a GCS inhibitor that has demonstrated CNS access (Genz-682452) reduced the accumulation of GL1 and GM2, as well as a variety of disease-associated substrates in the liver and brain, and support the development of SRT for the treatment of gangliosidoses, particularly in patients with residual enzyme activity.
Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy
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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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An evidence-based review of the potential benefits of taliglucerase alfa in the treatment of patients with Gaucher disease
TLDR
Taliglucerase alfa is a valuable new treatment modality for the non-neuronopathic manifestations of Gaucher disease and is expected that this new treatment would reduce the costs of therapy.
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TLDR
Data indicate that an orally available antagonist of GCS that has CNS access is effective at attenuating several of the neuropathologic and behavioral manifestations associated with mouse models of neuronopathic GD, and holds promise as a potential therapeutic approach for patients with type-3 GD.
Substrate reduction therapy of glycosphingolipid storage disorders
TLDR
Oral administration of an inhibitor of glucosylceramide synthesis (N-butyldeoxynojirimycin, registered in Europe since 2002 as miglustat (Zavesca), is effective in reversing clinical symptoms in type I Gaucher patients with mild to moderate disease manifestations.
Review of miglustat for clinical management in Gaucher disease type 1
  • C. Ficicioglu
  • Medicine
    Therapeutics and clinical risk management
  • 2008
TLDR
The results of clinical studies and use of miglustat as a therapeutic agent in patients with type I Gaucher disease are discussed.
N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice
TLDR
NB-DGJ is effective in reducing total brain ganglioside and GM2 content at early neonatal ages and caused a slight, but significant elevation in brain sialidase activity in the Sandhoff disease (Hexb(-/-) mice.
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