To determine the efficacy of ASOs in synucleinopathies, we used rat and mouse aSyn preformed fibril (PFF) transmission models, which replicate aspects of human PD progression, including seeding and aggregate deposition of endogenous aSyn, reduced striatal dopamine, dopaminergic cell dysfunction (tyrosine hydroxylase [TH] loss) in the substantia nigra (SN), and motor dysfunction (29, 30). Here, TH is linked to Parkinson disease.