Upregulation of expression from the FRDA genomic locus for the therapy of Friedreich ataxia

Abstract

Background: Friedreich ataxia is a slowly progressive neurodegenerative disease caused by reduced expression of frataxin as a result of a GAA repeat expansion in the first intron of the FRDA gene. We report here the development of a sensitive cellular assay for frataxin expression from the intact FRDA locus that should facilitate the identification of potentially therapeutic pharmacological agents to treat Friedreich ataxia. Methods: PAC and BAC clones containing the entire human FRDA functional genomic sequence were identified and shown to express FRDA mRNA. The GET Recombination system was used to insert cassettes consisting of the gene encoding EGFP linked to a kanamycin/neomycin resistan..