Monitoring the 3-year efficacy of enzyme replacement therapy in fabry disease by repeated skin biopsies

Beth L. Thurberg, H. Randolph Byers, Scott R. Granter, Robert G. Phelps, Ronald E. Gordon, Michael O'Callaghan

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


The earliest clinical signs of Fabry disease often manifest as dermatologic disturbances such as angiokeratomata, hypohidrosis, acroparesthesias, and impaired thermal and vibration detection. These disturbances are caused by cellular globotriaosylceramlde accumulation in the skin due to deficient lysosomal α-galactosidase A activity. In this histologic study, we analyzed pre- and post-treatment dermatologic biopsies from 58 Fabry patients enrolled in a 5 mo, Phase 3 double-blind, randomized, placebo-controlled trial followed by a 30 mo open label extension study of recombinant human α-galactosidase A (r-hαGalA), administered i.v. at 1 mg per kg every 2 wk. Baseline evaluations revealed globotriaosylceramide in multiple dermal cell types (vascular endothelial cells, vascular smooth muscle cells, perineurium). Five months of r-hαGalA treatment in the Phase 3 trial resulted in complete clearance of globotriaosylceramide from the superficial capillary endothelium in all treatment patients and in only 1 (3%) placebo patient (p<0.001). The placebo group achieved similar results after 6 mo of r-hαGalA in the open label trial. The capillary endothelium remained free of globotriaosylceramide for up to 30 mo into the extension study among 39 of 40 (98%) patients who underwent biopsies. Globotriaosylceramide clearance from deep vascular endothelial cells was similarly robust. Vascular smooth muscle cells and perineurium demonstrated moderate clearance. These findings suggest that long-term treatment with r-hαGalA may halt the progression of pathology and prevent the dermatologic disturbances in Fabry patients, and that periodic dermal biopsies can serve as a reliable monitor of sustained efficacy.

Original languageEnglish
Pages (from-to)900-908
Number of pages9
JournalJournal of Investigative Dermatology
Issue number4
StatePublished - Apr 2004


  • Angiokeratomas
  • Globotriaosylceramide
  • Lysosomal storage disease
  • Phase 3 trial
  • α-galactosidase A


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