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 I Finkelstein, John B Furness
J Parkinsons Dis | Published : 2021
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..View full abstract