Screening for pharmacological chaperones in Fabry disease.
Biochem Biophys Res Commun
; 359(1): 168-73, 2007 Jul 20.
Article
en En
| MEDLINE
| ID: mdl-17532296
ABSTRACT
As a prerequisite for clinical trials of pharmacological chaperone therapy (PCT) for Fabry disease, we developed a rapid screening assay for enhancement of endogenous alpha-galactosidase A (alpha-Gal A) in patient-derived cells. We used a T-cell based system to screen 11 mutations causing Fabry disease for enhanceability using 1-deoxygalactonojirimycin (DGJ). When patient-derived T-cells were grown in the presence of DGJ, alpha-Gal A activity increased to more than 50% of normal in several mutations but was unaffected in others. In addition to the mutation R301Q, reported previously, A97V, R112H, R112C, A143T, and L300P were enhanceable, but R356W, G132R, A143P, R220X, and 30delG were not. The level of alpha-Gal A activity achieved provides a basis for the therapeutic trial of DGJ in patients with similarly enhanceable enzyme. This assay method has general utility in other disorders in assessing the degree of enhancement of activity of mutated proteins by PCT.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Bioensayo
/
Leucocitos Mononucleares
/
Linfocitos T
/
Enfermedad de Fabry
/
Alfa-Galactosidasa
/
Chaperonas Moleculares
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos