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Pharmacological Chaperone Therapy for Fabry Disease

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Fabry Disease

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Abstract

Pharmacological chaperone therapy is an emerging therapeutic treatment for genetic disorders resulting from the improper folding of proteins. A large set of disease-causing missense mutations in Fabry disease result in the synthesis of improperly folded α-galactosidase A that are retarded in the endoplasmic reticulum (ER) and degraded in the ER-associated degradation pathway, although these proteins may be enzymologically active, if they could be properly transported to the lysosomes. Pharmacological chaperones increase the residual enzyme activity in patients by acting as a folding template in the ER to facilitate proper folding of mutant proteins, hence accelerating their transport out from the ER and reach to lysosomes. 1-Deoxygalactonojirimycin (DGJ, migalastat, Amigal™) is a pharmacological chaperone for Fabry disease. This chapter describes the protein misfolding phenotype of Fabry disease, the mechanism of pharmacological chaperone therapy for Fabry disease, and the clinical development of DGJ for treating Fabry disease.

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Author information

Authors and Affiliations

  1. Pfantastic Medical Research Institute, Cresskill, NJ, USA

    Jian-Qiang Fan

  2. Faculty of Medicine, Oita University, Oita, Japan

    Satoshi Ishii

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  1. Jian-Qiang Fan
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  2. Satoshi Ishii
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Correspondence to Jian-Qiang Fan .

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Editors and Affiliations

  1. , Shaare Zedek Medical Center, Gaucher Clinic, Bayit Street 12, Jerusalem, 91034, Israel

    Deborah Elstein

  2. , Shaare Zedek Medical Center, Genetics Unit, Bayit Street 12, Jerusalem, 91031, Israel

    Gheona Altarescu

  3. University of Mainz, Children's Hospital, Langenbeckstrasse 1, Mainz, 55131, Germany

    Michael Beck

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Fan, JQ., Ishii, S. (2010). Pharmacological Chaperone Therapy for Fabry Disease. In: Elstein, D., Altarescu, G., Beck, M. (eds) Fabry Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9033-1_29

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  • DOI: https://doi.org/10.1007/978-90-481-9033-1_29

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  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-9032-4

  • Online ISBN: 978-90-481-9033-1

  • eBook Packages: MedicineMedicine (R0)

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