BACKGROUND: Fabry disease (FD) is a genetic disorder resulting from deficiency 
of the lysosomal enzyme α-galactosidase A (α-Gal A) which leads to 
globotriaosylceramide (GL-3) accumulation in multiple tissues. We report on the 
safety and pharmacodynamics of migalastat hydrochloride, an investigational 
pharmacological chaperone given orally every other day (QOD) to females with FD.
METHODS: This was an open-label, uncontrolled, Phase 2 study of 12 weeks with 
extension to 48 weeks in nine females with FD. Doses of 50mg, 150 mg and 250 mg 
were given QOD. At multiple time points, α-Gal A activity and GL-3 levels were 
quantified in blood cells, kidney and skin. GL-3 levels were also evaluated 
through skin and renal histology. Each individual GLA mutation was 
retrospectively categorized as being amenable or not to migalastat HCl based on 
an in vitro α-Gal A transfection assay developed in human embryonic kidney 
(HEK)-293 cells.
RESULTS: Migalastat HCl was generally well tolerated. Patients with amenable 
mutations seem to demonstrate greater pharmacodynamic response to migalastat HCl 
compared to patients with non-amenable mutations. The greatest declines in urine 
GL-3 were observed in the three patients with amenable GLA mutations that were 
treated with 150 or 250 mg migalastat HCl QOD. Additionally, these three 
patients all demonstrated decreases in GL-3 inclusions in kidney peri-tubular 
capillaries.
CONCLUSIONS: Migalastat HCl is a candidate oral pharmacological chaperone that 
provides a potential novel genotype-specific treatment for FD. Treatment 
resulted in GL-3 substrate decrease in female patients with amenable GLA 
mutations. Phase 3 studies are ongoing.