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In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
10:16

In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease

Published on: December 20, 2017

Efficacy of enzyme replacement therapy in Fabry disease

F Barbey1, D Hayoz, U Widmer

  • 1Division of Nephrology, Lausanne University Hospital, Switzerland. frederic.barbey@chuv.hospvd.ch

Current Medicinal Chemistry. Cardiovascular and Hematological Agents
|August 24, 2004
PubMed

Insights

Enzyme replacement therapy is available for Fabry disease, a genetic disorder caused by alpha-galactosidase A deficiency. Agalsidase alfa and beta offer treatment options, but glycosylation differences may impact their effectiveness and safety.

Area of Science:

  • Biochemistry
  • Genetics
  • Pharmacology

Background:

  • Fabry disease is a rare, X-linked lysosomal storage disorder resulting from alpha-galactosidase A deficiency.
  • This deficiency causes globotriaosylceramide accumulation, leading to organ damage and premature death.
  • Enzyme replacement therapy (ERT) is a recent treatment approach for Fabry disease.

Purpose of the Study:

  • To outline the clinical aspects of Fabry disease, including signs, symptoms, and diagnosis.
  • To review the development of agalsidase alfa and agalsidase beta, the two available ERTs.
  • To explore how glycosylation differences between these ERTs might influence their clinical outcomes.

Main Methods:

  • Review of clinical signs, symptoms, and diagnostic criteria for Fabry disease.
  • Examination of the development and production of agalsidase alfa and agalsidase beta.
  • Analysis of the impact of post-translational glycosylation on protein therapeutics.

Main Results:

  • Agalsidase alfa and beta share the same amino acid sequence as native alpha-galactosidase A but differ in glycosylation.
  • Glycosylation affects pharmacokinetics, biodistribution, efficacy, and tolerability of protein therapeutics.
  • Differences in glycosylation may explain variations in dosing, clinical effects, and safety profiles between the two ERTs.

Conclusions:

  • Agalsidase alfa and beta represent significant advancements in Fabry disease treatment.
  • Glycosylation is a critical factor influencing the therapeutic performance of ERTs.
  • Further research into glycosylation is essential for optimizing Fabry disease management and developing future therapies.

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