Journal article

ATH434 Reverses Colorectal Dysfunction in the A53T Mouse Model of Parkinson's Disease

Shanti Diwakarla, Rachel M McQuade, Remy Constable, Olivia Artaiz, Enie Lei, Kevin J Barnham, Paul A Adlard, Robert A Cherny, Madeleine R Di Natale, Hongyi Wu, Xin-Yi Chai, Victoria A Lawson, David Finkelstein, John B Furness



BACKGROUND: Gastrointestinal (GI) complications, that severely impact patient quality of life, are a common occurrence in patients with Parkinson's disease (PD). Damage to enteric neurons and the accumulation of alpha-synuclein in the enteric nervous system (ENS) are thought to contribute to this phenotype. Copper or iron chelators, that bind excess or labile metal ions, can prevent aggregation of alpha-synuclein in the brain and alleviate motor-symptoms in preclinical models of PD. OBJECTIVE: We investigated the effect of ATH434 (formally PBT434), a small molecule, orally bioavailable, moderate-affinity iron chelator, on colonic propulsion and whole gut transit in A53T alpha-synuclein trans..

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Awarded by National Health and Medical Research Council

Funding Acknowledgements

The Florey Institute of Neuroscience and Mental Health acknowledge the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant. This work was supported by funding from the National Health and Medical Research Council (grant APP1145686). ATH434 was generously supplied by Alterity Therapeutics.