Journal article

Friedreich's ataxia induced pluripotent stem cell-derived cardiomyocytes display electrophysiological abnormalities and calcium handling deficiency

Duncan E Crombie, Claire L Curl, Antonia JA Raaijmakers, Priyadharshini Sivakumaran, Tejal Kulkarni, Raymond CB Wong, Itsunari Minami, Marguerite V Evans-Galea, Shiang Y Lim, Lea Delbridge, Louise A Corben, Mirella Dottori, Norio Nakatsuji, Ian A Trounce, Alex W Hewitt, Martin B Delatycki, Martin F Pera, Alice Pebay



We sought to identify the impacts of Friedreich's ataxia (FRDA) on cardiomyocytes. FRDA is an autosomal recessive degenerative condition with neuronal and non-neuronal manifestations, the latter including progressive cardiomyopathy of the left ventricle, the leading cause of death in FRDA. Little is known about the cellular pathogenesis of FRDA in cardiomyocytes. Induced pluripotent stem cells (iPSCs) were derived from three FRDA individuals with characterized GAA repeats. The cells were differentiated into cardiomyocytes to assess phenotypes. FRDA iPSC- cardiomyocytes retained low levels of FRATAXIN (FXN) mRNA and protein. Electrophysiology revealed an increased variation of FRDA- cardiomyo..

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Funding Acknowledgements

This work was supported by grants from the Friedrich Ataxia Research Alliance (USA, Ireland and Australasia), a National Health and Medical Research Council (NHMRC) Career Development Award Fellowship (AP), a NHMRC-CSL Gustav Nossal postgraduate research scholarship (DEC), a NHMRC Practitioner Fellowship (AWH), Australian Research Council (ARC) Future Fellowships (AP and MD), a Cranbourne Fellowship (RCBW), an ARC special Initiative Stem Cells Australia grant (MD, MPF, AP), a National Stem Cell Foundation of Australia grant (AP) and Operational Infrastructure Support from the Victorian Government.