Current and emerging therapies for Parkinson’s disease: advances toward disease modification

Abstract

Parkinson’s disease is a complex, progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to motor and non-motor symptoms. While symptomatic treatments such as levodopa and monoamine oxidase-B inhibitors offer short-term relief, they do not halt disease progression. In recent years, significant advances have been made in understanding the molecular mechanisms underlying Parkinson’s disease, including alpha-synuclein aggregation, mitochondrial dysfunction, neuroinflammation, and lysosomal impairment. These insights have spurred the development of targeted therapeutic strategies aimed at modifying disease progression. This review comprehensively explores emerging approaches such as gene and cell therapies, LRRK2 inhibitors, alpha-synuclein immunotherapy, and gut microbiota modulation. We also discuss the therapeutic potential of mitophagy activators, digital biomarkers, and neuromodulation techniques. Each therapeutic strategy is critically evaluated in the context of underlying pathophysiological mechanisms. Special attention is given to recent clinical trials (2023–2025), translational gaps, and the potential of personalized medicine in Parkinson’s disease management. Furthermore, we examine the integration of multi-omics data and digital tools in advancing precision therapeutics. Overall, this review highlights current challenges and future prospects in the journey toward disease-modifying interventions that move beyond symptomatic relief.