Gene therapy for Parkinson’s disease: current landscape, translational challenges, and future directions

Gene therapy for PD is transitioning from symptomatic modulation toward targeted molecular correction. Clinical trials have validated durable, neuron specific expression using AAV and lentiviral vectors and demonstrated target engagement across dopamine synthesis, trophic support, and genetic mutation - specific strategies. Persistent challenges include limited vector biodistribution, reduced retrograde transport in advanced disease, immune variability, and surgical infrastructure requirements. Overcoming these via engineered capsids, delivery optimization, and validated biomarkers will enable precision, stage‑specific interventions.