Oral chaperone therapy migalastat for treating Fabry disease: enzymatic response and serum biomarker changes after one year.

Long-term effects of migalastat therapy in clinical practice are currently unknown. We evaluated migalastat efficacy and biomarker changes in a prospective, single-center study on 14 patients with Fabry disease (55 +/- 14years; 11 men). After 1year of open-label migalastat therapy, patients showed significant changes in alpha-galactosidase-A activity (0.06-0.2nmol/minute/mg protein; P=0.001), left ventricular myocardial mass index (137-130g/m(2); P=0.037), and serum creatinine (0.94-1.0mg/dL; P=0.021), accounting for deterioration in estimated glomerular filtration rate (87-78mL/minute/1.73m(2); P=0.012). The enzymatic increase correlated with myocardial mass reduction (r=-0.546; P=0.044) but not with renal function (r=-0.086; P=0.770). Plasma globotriaosylsphingosine was reduced in therapy-naive patients (10.9-6.0ng/mL; P=0.021) and stable (9.6-12.1ng/mL; P=0.607) in patients switched from prior enzyme-replacement therapy. These first real-world data show that migalastat substantially increases alpha-galactosidase-A activity, stabilizes related serum biomarkers, and improves cardiac integrity in male and female patients with amenable Fabry disease mutations.