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Macrophages as Therapeutic Targets in Lysosomal Storage Disorders

  • Chapter
The Macrophage as Therapeutic Target

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 158))

Abstract

Gaudier disease (lysosomal glucocerebrosidase deficiency) is a rare inborn error of metabolism. The type 1 variant is characterised by lysosomal storage of glucosylceramide in tissue macrophages exclusively. The accumulation of storage cells (Gaucher cells) results in pronounced hepatosplenomegaly, haematological abnormalities and deterioration of the skeleton. Type 1 Gaucher disease should be considered as a true macrophage disorder. Specific markers for Gaucher cells, like a hitherto unknown chitinase, have been identified and are commonly used to monitor progression of disease and efficacy of therapies. A spectacular correction in clinical symptoms of type 1 patients can be accomplished by chronic intravenous administration of human glucocerebrosidase containing glycans with terminal mannose-moieties. Currently, about 3,000 patients are treated worldwide with recombinant enzyme (Cerezyme). Enzyme replacement therapy (ERT) is not able to prevent glucosylceramide accumulation in the brain of patients suffering from the severe type 2 variant of Gaucher disease. Recently, oral administration of N-butyl-deoxynojirimycin has been registered in the EU for treatment of type 1 Gaucher patients that are unsuitable for ERT. The iminosugar inhibits the synthesis of glucosylceramide and thus prevents massive accumulation of the lipid.

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Authors and Affiliations

  1. Department of Biochemistry and Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    J. M. Aerts, C. Hollak, R. Boot & A. Groener

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  1. J. M. Aerts
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  2. C. Hollak
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  3. R. Boot
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  4. A. Groener
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Editors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, OX1 3RE, Oxford, UK

    Siamon Gordon

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Aerts, J.M., Hollak, C., Boot, R., Groener, A. (2003). Macrophages as Therapeutic Targets in Lysosomal Storage Disorders. In: Gordon, S. (eds) The Macrophage as Therapeutic Target. Handbook of Experimental Pharmacology, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55742-2_11

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  • DOI: https://doi.org/10.1007/978-3-642-55742-2_11

  • Publisher Name: Springer, Berlin, Heidelberg

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