Journal article

Abnormalities of mitochondrial dynamics and bioenergetics in neuronal cells from CDKL5 deficiency disorder

Nicole J Van Bergen, Sean Massey, Tegan Stait, Molly Ellery, Boris Reljic, Luke E Formosa, Anita Quigley, Mirella Dottori, David Thorburn, David A Stroud, John Christodoulou



CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental disorder caused by pathogenic variants in the Cyclin-dependent kinase-like 5 (CDKL5) gene, resulting in dysfunctional CDKL5 protein. It predominantly affects females and causes seizures in the first few months of life, ultimately resulting in severe intellectual disability. In the absence of targeted therapies, treatment is currently only symptomatic. CDKL5 is a serine/threonine kinase that is highly expressed in the brain, with a critical role in neuronal development. Evidence of mitochondrial dysfunction in CDD is gathering, but has not been studied extensively. We used human patient-derived induced pluripotent stem cells with a ..

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Awarded by Orphan Disease Center of the University of Pennsylvania

Awarded by Australian National Health & Medical Research Council (NHMRC)

Funding Acknowledgements

T The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. Funding to NVB was provided by the Foundation for Children Project Grant (2018-16), Murdoch Children's Research Institute Strategic Pilot Project in Stem Cell and Genomic Medicine Research Grant, Million Dollar Bike Ride pilot grant from the Orphan Disease Center of the University of Pennsylvania (MDBR-20-106-CDKL5) and the CDKL5 Forum Junior Fellowship from the Loulou Foundation (NVB). ME was supported by an Murdoch Children's Research Institute student scholarship. DS is supported by Australian National Health & Medical Research Council (NHMRC) grants GNT1140851 and GNT1140906. Bio21 Mass Spectrometry instrumentation is supported by a large equipment grant from the Mito Foundation, Australia. AQ is funded by an RMIT Vice Chancellor's Senior Fellowship and a St Vincent's Hospital Australia Endowment Grant. The Chair in Genomic Medicine awarded to JC is generously supported by The Royal Children's Hospital Foundation.