Proof of concept of treatment with novel hydroxypyridinone iron chelators in a non-clinical model of Parkinson’s disease
The two iron chelators will be studied in a chronic, toxin-induced pre-clinical model of PD, which features selective degeneration of dopaminergic neurons, brain iron accumulation, and oxidative stress. Improvement in motor function in response to treatment will be assessed using multiple behavioural tests. Changes in levels of dopamine, free iron levels in the substantia nigra and markers of oxidative stress, and protective effects on dopaminergic neurons will be examined and correlated with behavioral outcomes. The therapeutic effect of these novel compounds will be compared to deferiprone, a structurally related iron chelator with neuroprotective properties in pre-clinical models of PD.