Low-Dose N-Butyldeoxynojirimycin (OGT 918) for Type I Gaucher Disease

Heitner, Rene; Elstein, Deborah; Aerts, Johannes M. F. G.; Weely, Sonja van; Zimran, Ari

doi:10.1006/bcmd.2002.0497

Cited by 93 publications

(60 citation statements)

References 3 publications

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“…While ERT forms the mainstay of treatment for type I GD, the iminosugar miglustat (Zavesca®; Actelion Pharmaceuticals Ltd.) represents an alternative treatment strategy - substrate reduction therapy [63]. In clinical trials in ERT-naïve adults with type I GD, miglustat treatment was effective in reducing liver and spleen volume and increasing hemoglobin concentration and platelet count during 12-36 months of treatment [64,65,66,67]. Miglustat has also been shown to improve bone mineral density in both the trabecular and cortical bones [68].…”

Section: Therapeutics Of Gdmentioning

confidence: 99%

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

Dandana¹,

Khelifa²,

Chahed³

et al. 2015

Pathobiology

114

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We present a brief review of Gaucher disease (GD), the most common lysosomal storage disease. GD is a rare autosomal recessive disorder characterized by the defective function of the catabolic enzyme β-glucocerebrosidase (GBA), leading to an accumulation of its substrate, glucocerebroside. Clinical signs and symptoms include neurological dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia and thrombocytopenia. Enzyme replacement therapy with recombinant GBA is the mainstay of treatment for GD, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.

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Section: Therapeutics Of Gdmentioning

confidence: 99%

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

Dandana¹,

Khelifa²,

Chahed³

et al. 2015

Pathobiology

114

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“…Continual improvements in organomegaly and hematological abnormalities were noticed between 6 and 12 months of treatment, although the extent of the response is less than that generally seen with ERT. The therapeutic effect is dose dependent, and a lower dose of N-butyl-DNJ (50 mg three times daily) is far less effective [80]. Unlike Cerezyme, Zavesca administered orally appears to cross the blood-brain barrier.…”

Section: Substrate Reduction Therapymentioning

confidence: 99%

Therapeutic strategies to ameliorate lysosomal storage disorders – a focus on Gaucher disease

Sawkar

D’Haeze

Kelly

2006

Cell. Mol. Life Sci.

120

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The lysosomal storage disorders encompass more than 40 distinct diseases, most of which are caused by the deficient activity of a lysosomal hydrolase leading to the progressive, intralysosomal accumulation of substrates such as sphingolipids, mucopolysaccharides, and oligosaccharides. Here, we primarily focus on Gaucher disease, one of the most prevalent lysosomal storage disorders, which is caused by an impaired activity of glucocerebrosidase, resulting in the accumulation of the glycosphingolipid glucosylceramide in the lysosomes. Enzyme replacement and substrate reduction therapies have proven effective for Gaucher disease cases without central nervous system involvement. We discuss the promise of chemical chaperone therapy to complement established therapeutic strategies for Gaucher disease. Chemical chaperones are small molecules that bind to the active site of glucocerebrosidase variants stabilizing their three-dimensional structure in the endoplasmic reticulum, likely preventing their endoplasmic reticulum-associated degradation and allowing their proper trafficking to the lysosome where they can degrade accumulated substrate to effectively ameliorate Gaucher disease.

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“…Evidence for a dose-related effect of N B-DNJ was shown in a subsequent trial where patients were given 50 mg of the drug three times daily. Under these circumstances, modest reductions in liver and spleen volumes (5.9 and 4.5 per cent respectively after 6 months of treatment) were demonstrated [58].…”

Section: Clinical Studies Of Nb-dnj (Miglustat) In Gaucher Disease Anmentioning

confidence: 94%

“…Impaired mental function has not subsequently been noted in follow-up monitoring, further clinical trials or pharmacovigilance reports [56][57][58][59].…”

Section: Adverse Effectsmentioning

confidence: 99%