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

@article{Cox2003TheRO,
  title={The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: A position statement},
  author={Timothy M. 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={2003},
  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… 
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241 Citations

Design and synthesis of iminosugar-based inhibitors of glucosylceramide synthase: the search for new therapeutic agents against Gaucher disease

Imiglucerase and its use for the treatment of Gaucher's disease

Imiglucerase is safe and well tolerated and corrects the hepatic, splenic, hematologic and bone abnormalities observed with types 1 and 3 Gaucher's disease effectively and enhances health-related quality of life.

Substrate Reduction Therapy for Sandhoff Disease through Inhibition of Glucosylceramide Synthase Activity.

Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy

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.

Force majeure: therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease.

CNS-accessible Inhibitor of Glucosylceramide Synthase for Substrate Reduction Therapy of Neuronopathic Gaucher Disease

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

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, Biology
    Therapeutics and clinical risk management
  • 2008
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

N-butyldeoxynojirimycin treatment restores the innate fear response and improves learning in mucopolysaccharidosis IIIA mice.

...

References

SHOWING 1-10 OF 47 REFERENCES

Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis

Substrate reduction therapy of glycosphingolipid storage disorders

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.

N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis.

Enzyme Therapy in Type 1 Gaucher Disease: Comparative Efficacy of Mannose-Terminated Glucocerebrosidase from Natural and Recombinant Sources

To determine the efficacy of recombinant glucocerebrosidase, a randomized, double-blind, parallel trial with mannose-terminated glu cocerebosidase (alglucerase, Ceredase) from human placenta and the human enzyme that is produced in Chinese hamster ovary cells and deglycosylated to expose mannosed residues in the oligosaccharide chains was done.

Failure of Alglucerase Infused into Gaucher Disease Patients to Localize in Marrow Macrophages

Even with the large bolus doses used for the treatment of Gaucher disease by some, scarcely any β-glucosidase activity was found in marrow samples; the amount of the enzyme was much less than would have been anticipated had the enzyme been evenly distributed to all body cells.

The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases.

  • M. TierneyJ. Pottage J. Sherman
  • Medicine
    Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association
  • 1995
The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates.

Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease.

Intravenous administration of macrophage-targeted glucocerebrosidase produces objective clinical improvement in patients with type 1 Gaucher's disease.

The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3.

Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients and the mean SC-48334 steady-state trough level was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV).

Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease.

It is concluded that OGT 918 was safe and effective at 50 mg TID, but shows dose dependency in ameliorating parameters of Gaucher disease relative to the results noted in the seminal trial; there was no improvement in the rate of hematological response and no reduction in side effects.

Mutation analysis of the acid beta-glucosidase gene in a patient with type 3 Gaucher disease and neutralizing antibody to alglucerase.