Fabry disease: Clinical spectrum and evidence-based enzyme replacement therapy

Robert J. Desnick, Maryam Banikazemi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The clinical spectrum of Fabry disease, an X-linked lysosomal storage disorder due to α-galactosidase A (α-Gal A) deficiency, has been expanded beyond the classic phenotype to include the recently recognized later-onset "cardiac" and "renal" variants. The clinical manifestations in each of these disease subtypes are presented with particular emphasis on early recognition among pediatric patients as well as identification of unrecognized patients diagnosed as hypertrophic cardiomyopathy or in renal dialysis clinics. Previously, treatment of patients with Fabry disease was limited to palliative care of the excruciating pain, cardiac and cerebrovascular manifestations, and renal failure. Recently, Fabry-specific enzyme replacement therapy (ERT) with recombinant α-Gal A (Fabrazyme®) has proven safe and effective. The preclinical, Phase 1/2 and multicenter, double-blind, randomized, placebo-controlled Phase 3 and 4 trials provided the evidence for the safety and efficacy of Fabrazyme® treatment. The preclinical and Phase 1/2 studies demonstrated that enzyme delivery to various tissues and GL-3 clearance were dose-dependent. The Phase 3 clinical trial and 3-year extension study provided long-term data documenting the safety and effectiveness of 1 mg/kg of Fabrazyme® for this disease. Finally, the "top-line" data from the Phase 4 trial indicates that in patients with mildly to moderately advanced renal disease, Fabrazyme® can slow the progression of renal, cardiac, and cerebrovascular events taken together or individually. The Phase 4 trial results also emphasize the importance of early treatment. In sum, these clinical trials provide the evidence-based safety and efficacy of Fabrazyme® replacement therapy for Fabry disease.

Original languageEnglish
Pages (from-to)S172-S185
JournalNephrologie et Therapeutique
Volume2
Issue numberSUPPL. 2
StatePublished - Jan 2006
Externally publishedYes

Keywords

  • Clinical spectrum
  • Enzyme replacement therapy
  • Fabrazyme*
  • Fabry disease
  • α-Galactosidase A

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