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Cardiac microvascular pathology in Fabry disease: evaluation of endomyocardial biopsies before and after enzyme
Beth L Thurberg1, John T Fallon, Richard Mitchell
1Department of Pathology, Genzyme Corporation, Cambridge, MA, USA. Beth.Thurberg@genzyme.com
Circulation
|May 6, 2009
Summary
Recombinant human alpha-galactosidase A effectively clears globotriaosylceramide (GL-3) deposits from heart microvasculature in Fabry disease patients, halting disease progression.
Area of Science:
- Cardiovascular Medicine
- Genetics and Inherited Diseases
- Lysosomal Storage Disorders
Background:
- Fabry disease involves globotriaosylceramide (GL-3) accumulation due to alpha-galactosidase A deficiency.
- Cardiovascular complications like atherosclerosis and hypertrophy occur in Fabry patients.
Purpose of the Study:
- To evaluate the efficacy of recombinant human alpha-galactosidase A in clearing GL-3 deposits in Fabry disease patients.
- To assess the long-term impact of treatment on cardiovascular pathology.
Main Methods:
- Analysis of endomyocardial biopsies from 58 Fabry patients in a Phase 3 trial and open-label extension.
- Comparison of GL-3 levels before and after treatment with recombinant human alpha-galactosidase A versus placebo.
Main Results:
- Five months of treatment achieved complete microvascular GL-3 clearance in 72% of patients, versus 3% for placebo.
- No GL-3 clearance was observed in cardiomyocytes during the initial trial.
- Capillary endothelium remained GL-3 free for up to 60 months in some patients.
Conclusions:
- Long-term recombinant human alpha-galactosidase A treatment may halt vascular pathology progression in Fabry disease.
- This histopathological study provides guidance for clinicians and pathologists managing Fabry patients.
