Fabry disease Enzyme Enhancement on migalastat Study: FEES

Area of Science:

• Biochemistry
• Genetics
• Pharmacology

Background:

• Limited data exists on the in vivo alpha-galactosidase A (α-Gal-A) response in Fabry disease patients treated with migalastat.
• Fabry disease is a rare genetic disorder characterized by deficient α-Gal-A activity.

Purpose of the Study:

• To evaluate changes in α-Gal-A activity, lyso-Gb3 levels, and other biomarkers in Fabry patients receiving migalastat.
• To assess the in vivo efficacy of migalastat in a cohort of Fabry disease patients.

Main Methods:

• Single-center study evaluating 79 Fabry disease patients (48 males, 31 females) receiving migalastat.
• Analysis of leukocyte and plasma α-Gal-A activity, plasma lyso-Gb3, and dried blood spot (DBS) lyso-Gb3.
• Genotyping, including the common N215S variant, was performed.

Main Results:

• Leukocyte α-Gal-A showed a positive change from baseline in both males and females, with varying median increases.
• Cross-sectional analysis confirmed leukocyte α-Gal-A enhancement in patients with N215S and other genotypes.
• Plasma and DBS lyso-Gb3 levels showed a strong correlation at baseline and post-treatment (r=0.77 and r=0.96, respectively).

Conclusions:

• Migalastat treatment led to enhanced leukocyte α-Gal-A activity in Fabry disease patients.
• Plasma and DBS lyso-Gb3 levels correlated well, indicating DBS utility for disease monitoring.
• The findings support migalastat's role in improving α-Gal-A activity in Fabry disease.