Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease

@article{Ashe2015EfficacyOE,
  title={Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease},
  author={Karen M. Ashe and Eva Budman and Dinesh S. Bangari and Craig S. Siegel and Jennifer B. Nietupski and Bing Wang and Robert J. Desnick and Ronald K. Scheule and John P. Leonard and Seng H. Cheng and John Marshall},
  journal={Molecular Medicine},
  year={2015},
  volume={21},
  pages={389-399}
}
Fabry disease, an X-linked glycosphingolipid storage disorder, is caused by the deficient activity of α-galactosidase A (α-Gal A). This results in the lysosomal accumulation in various cell types of its glycolipid substrates, including globotriaosylceramide (GL-3) and lysoglobotriaosylceramide (globotriaosyl lysosphingolipid, lyso-GL-3), leading to kidney, heart, and cerebrovascular disease. To complement and potentially augment the current standard of care, biweekly infusions of recombinant… 
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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.
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Precision medicine in Fabry disease.
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Therapeutic options for Fabry disease are discussed, with a special focus on precision medicine, accounting for individual variability in genetic mutations, Gb3 and lyso-Gb3 levels, allowing physicians to predict more accurately which prevention and treatment strategy is best for which patient.
Treatment of Anderson-Fabry disease.
TLDR
The current treatment of Anderson-Fabry disease is represented by enzyme replacement therapy (ERT) and oral pharmacological chaperone and future treatments are based on new strategic approaches as stem cell-based therapy, pharmacological approaches chaperones, mRNA therapy, viral gene therapy.
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An overview of the clinical picture in FD patients, diagnostic confirmation, and interdisciplinary clinical management of FD is provided and the focus is on current and future therapeutic options.
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