AUTHOR=Sandi Chiranjeevi , Sandi Madhavi , Anjomani Virmouni Sara , Al-Mahdawi Sahar , Pook Mark A. 

TITLE=Epigenetic-based therapies for Friedreich ataxia

JOURNAL=Frontiers in Genetics

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2014.00165

DOI=10.3389/fgene.2014.00165

ISSN=1664-8021

ABSTRACT=<p>Friedreich ataxia (FRDA) is a lethal autosomal recessive neurodegenerative disorder caused primarily by a homozygous GAA repeat expansion mutation within the first intron of the <italic>FXN</italic> gene, leading to inhibition of <italic>FXN</italic> transcription and thus reduced frataxin protein expression. Recent studies have shown that epigenetic marks, comprising chemical modifications of DNA and histones, are associated with <italic>FXN</italic> gene silencing. Such epigenetic marks can be reversed, making them suitable targets for epigenetic-based therapy. Furthermore, since FRDA is caused by insufficient, but functional, frataxin protein, epigenetic-based transcriptional re-activation of the <italic>FXN</italic> gene is an attractive therapeutic option. In this review we summarize our current understanding of the epigenetic basis of <italic>FXN</italic> gene silencing and we discuss current epigenetic-based FRDA therapeutic strategies.</p>