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Clinical Trial
. 2002 Jun 18:2:4.
doi: 10.1186/1471-2377-2-4.

Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease

David F Moore  1 , Gheona Altarescu, Peter Herscovitch, Raphael Schiffmann
Affiliations
Clinical Trial

Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease

David F Moore et al. BMC Neurol. .

Abstract

Background: Fabry disease is a lysosomal X-linked enzyme deficiency of alpha-galactosidase A associated with an increased mortality and morbidity due to renal failure, cardiac disease and early onset stroke.

Methods: We examined the functional blood flow response of the brain after visual stimulation (reversing checkerboard pattern), and cerebral vasoreactivity following acetazolamide (15 mg/kg) with [15O]H2O and positron emission tomography (PET) in Fabry disease. Twenty-six hemizygous patients (age range 19-47 years) were enrolled in a randomized double-blind placebo-controlled 6-month trial of enzyme replacement therapy administered by intravenous infusion every two weeks. Regional cerebral blood flow (rCBF) was measured with PET at the beginning and end of the trial.

Results: Fabry patients had a significantly greater increase in rCBF following visual stimulation and acetazolamide challenge compared to controls. Visual reactivity was normal. The time for recovery of the cerebral vasculature following acetazolamide was prolonged in Fabry patients compared to controls. The abnormal rCBF response induced by visual stimulation and acetazolamide decreased significantly following enzyme replacement therapy, as did the prolonged recovery of the cerebral vasculature.

Conclusions: Enzyme replacement therapy reverses the exaggerated cerebrovascular response in Fabry disease.

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Figures

Figure 1
Figure 1
rCBF SPM{t} map of significantly increased blood flow in the Fabry group (n = 26) compared to the control group (n = 10) during visual stimulation. No significant rCBF elevation was found in the control group compared to Fabry patients at the same set-level of inference (results not shown).
Figure 2
Figure 2
Acetazolamide challenge rCBF SPM{t} map of significantly increased blood flow in the Fabry group (n = 26) compared to normal controls (n = 10). The rCBF at thirty minutes post-infusion of acetazolamide was significantly greater in Fabry patients in many brain regions, with a posterior predominance. No significant rCBF elevation at the same set-level of inference was found in the control group compared to Fabry patients (results not shown).
Figure 3
Figure 3
SPM{t} map of significantly lower rCBF in the ERT treatment group (n = 14) during visual stimulation compared to the placebo group (n = 11) in many regions throughout the brain.
Figure 4
Figure 4
SPM{t} map of significantly lower rCBF 30-minute following acetazolamide challenge in the ERT group (n = 13) compared to the placebo group (n = 9).
See this image and copyright information in PMC

References

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    1. Moore DF, Scott LJC, Gladwin MT, Altarescu G, Kaneski C, Suzuki K, Pease-Fye M, Ferri R, Brady RO, Herscovitch P, Schiffmann R. Regional Cerebral Hyper-Perfusion and Nitric Oxide Pathway Dysregulation in Fabry Disease: Reversal by Enzyme Replacement Therapy. Circulation. 2001;104:1506–1512. - PubMed

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