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Roberto Testi, Professor and Chair in ImmunologyPublished March 23, 2012

Abstract

Friedreich's ataxia (FRDA) is the most common hereditary ataxia, affecting approximately 3 in 100,000 individuals in Caucasian populations. It is caused by intronic GAA repeat expansions that hinder the expression of the FXN gene, resulting in defective levels of the mitochondrial protein frataxin. Sensory neurons in dorsal root ganglia (DRG) are particularly damaged by frataxin deficiency. There is no specific therapy for FRDA. Here we show that frataxin levels can be upregulated by interferon gamma (IFNgamma) in a variety of cell types, including primary cells derived from FRDA patients. IFNgamma appears to act largely through a transcriptional mechanism on the FXN gene. Importantly, in vivo treatment with IFNgamma increases frataxin expression in DRG neurons, prevents their pathological changes and ameliorates the sensorimotor performance in FRDA mice. These results disclose new roles for IFNgamma in cellular metabolism and have direct implications for the treatment of FRDA.

Hum. Mol. Genet.   Open source full text link