title: Epigenetic-based therapies for Friedreich ataxia.
abstract: 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 FXN gene, leading to inhibition of FXN transcription and thus reduced frataxin protein expression. Recent studies have shown that epigenetic marks, comprising chemical modifications of DNA and histones, are associated with FXN 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 FXN gene is an attractive therapeutic option. In this review we summarize our current understanding of the epigenetic basis of FXN gene silencing and we discuss current epigenetic-based FRDA therapeutic strategies.
authors.affiliation: Division of Biosciences, School of Health Sciences and Social Care, Brunel University London Uxbridge, UK.
authors.forename: Chiranjeevi
authors.initials: C
authors.lastname: Sandi
authors.affiliation: Division of Biosciences, School of Health Sciences and Social Care, Brunel University London Uxbridge, UK.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Sandi
authors.affiliation: Division of Biosciences, School of Health Sciences and Social Care, Brunel University London Uxbridge, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Anjomani Virmouni
authors.affiliation: Division of Biosciences, School of Health Sciences and Social Care, Brunel University London Uxbridge, UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Al-Mahdawi
authors.affiliation: Division of Biosciences, School of Health Sciences and Social Care, Brunel University London Uxbridge, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pook
keywords: DNA demethylation; FRDA; FXN; Friedreich ataxia; GAA repeat; HDAC inhibitor; HMTase inhibitor; frataxin