title: Cell and gene therapy for Friedreich ataxia: progress to date.
abstract: Neurodegenerative disorders such as Friedreich ataxia (FRDA) present significant challenges in developing effective therapeutic intervention. Current treatments aim to manage symptoms and thus improve quality of life, but none can cure, nor are proven to slow, the neurodegeneration inherent to this disease. The primary clinical features of FRDA include progressive ataxia and shortened life span, with complications of cardiomyopathy being the major cause of death. FRDA is most commonly caused by an expanded GAA trinucleotide repeat in the first intron of FXN that leads to reduced levels of frataxin, a mitochondrial protein important for iron metabolism. The GAA expansion in FRDA does not alter the coding sequence of FXN. It results in reduced production of structurally normal frataxin, and hence any increase in protein level is expected to be therapeutically beneficial. Recently, there has been increased interest in developing novel therapeutic applications like cell and/or gene therapies, and these cutting-edge applications could provide effective treatment options for FRDA. Importantly, since individuals with FRDA produce frataxin at low levels, increased expression should not elicit an immune response. Here we review the advances to date and highlight the future potential for cell and gene therapy to treat this debilitating disease.
authors.affiliation: 1 Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute , Parkville Victoria 3052, Australia .
authors.forename: Marguerite V
authors.initials: MV
authors.lastname: Evans-Galea
authors.forename: Alice
authors.initials: A
authors.lastname: Pébay
authors.forename: Mirella
authors.initials: M
authors.lastname: Dottori
authors.forename: Louise A
authors.initials: LA
authors.lastname: Corben
authors.forename: Sze Hwee
authors.initials: SH
authors.lastname: Ong
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lockhart
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D005621:Friedreich Ataxia / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D033581:Stem Cell Transplantation; D014161:Transduction, Genetic