Pharmacological Screening Using an FXN-EGFP Cellular Genomic Reporter Assay for the Therapy of Friedreich Ataxia
Lingli Li, Lucille Voullaire, Chiranjeevi Sandi, Mark A Pook, Panos A Ioannou, Martin B Delatycki, Joseph P Sarsero
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2013
Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay..View full abstract
Awarded by Muscular Dystrophy Association (USA)
Awarded by National Health and Medical Research Council (Australia)
This work was supported by the Muscular Dystrophy Association (USA) (grants 3657, 3725, 69033), the National Health and Medical Research Council (Australia) (grant 491234), the Friedreich's Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government's Operational Infrastructure Support Program. MBD is a National Health and Medical Research Council Practitioner Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.