The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat.

ABSTRACT:

Purpose

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Migalastat, a pharmacological chaperone, binds to specific mutant forms of α-galactosidase A to restore lysosomal activity.

Methods

A pharmacogenetic assay was used to identify the α-galactosidase A mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations were expressed in HEK-293 (HEK) cells; increases in α-galactosidase A activity were measured by a good laboratory practice (GLP)-validated assay (GLP HEK/Migalastat Amenability Assay). The predictive value of the assay was assessed based on pharmacodynamic responses to migalastat in phase II and III clinical studies.

Results

Comparison of the GLP HEK assay results in in vivo white

SUBMITTER: Benjamin ER 

PROVIDER: S-EPMC5392595 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature