title: Using human pluripotent stem cells to study Friedreich ataxia cardiomyopathy.
abstract: Friedreich ataxia (FRDA) is the most common of the inherited ataxias. It is an autosomal recessive disease characterised by degeneration of peripheral sensory neurons, regions of the central nervous system and cardiomyopathy. FRDA is usually due to homozygosity for trinucleotide GAA repeat expansions found within first intron of the FRATAXIN (FXN) gene, which results in reduced levels of the mitochondrial protein FXN. Reduced FXN protein results in mitochondrial dysfunction and iron accumulation leading to increased oxidative stress and cell death in the nervous system and heart. Yet the precise functions of FXN and the underlying mechanisms leading to disease pathology remain elusive. This is particularly true of the cardiac aspect of FRDA, which remains largely uncharacterized at the cellular level. Here, we summarise current knowledge on experimental models in which to study FRDA cardiomyopathy, with a particular focus on the use of human pluripotent stem cells as a disease model.
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Australia; Ophthalmology, Department of Surgery, The University of Melbourne, Australia.
authors.forename: Duncan E
authors.initials: DE
authors.lastname: Crombie
authors.affiliation: Department of Anatomy and Neurosciences, The University of Melbourne, Florey Neuroscience & Mental Health Institute, Walter and Eliza Hall Institute of Medical Research, Australia.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Pera
authors.affiliation: Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Department of Paediatrics, The University of Melbourne, Australia; School of Psychology and Psychiatry, Monash University, Australia; Clinical Genetics, Austin Health, Australia.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Australia; Ophthalmology, Department of Surgery, The University of Melbourne, Australia. Electronic address: apebay@unimelb.edu.au.
authors.forename: Alice
authors.initials: A
authors.lastname: Pébay
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology*; D002460:Cell Line; D005621:Friedreich Ataxia / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000473:pathology* / Q000502:physiology
keywords: Cardiomyopathy; FRATAXIN; Friedreich ataxia; Stem cells