The ASO-based study on Parkinson’s disease (PD), conducted in humanized rats and iPSC neurons from patients with PD, has yielded significant findings. The administration of the lead compound, ASO3, not only reduced monomeric and aggregated alpha-synuclein levels but also increased locomotor activity and enhanced olfactory function in animals, without causing side effects or neurotoxicity. Furthermore, ASO3 restored cytokine expression to wild-type levels, suggesting an immunomodulatory effect. Phosphoprotein multiplexing highlighted the restoration of activated signaling pathways, underscoring the potential of ASO3 in reversing PD pathology. Neurotransmitter measurements indicated subtle shifts toward normalization. Pharmacokinetic analysis of ASO3 revealed that it remained stable in the brains of rats for an extended period. Alongside a comprehensive bioinformatics analysis of RNAseq data, this study has helped assess the mechanisms of action of ASO3 and identify molecular biomarkers of PD. Overall, these results suggest that ASO3 is a promising therapeutic compound for tackling Parkinson’s disease.