Gene therapy for Parkinson's disease: current landscape, translational challenges, and future directions - PubMed
5 hours ago
- #Neurodegeneration
- #Parkinson's Disease
- #Gene Therapy
- Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss.
- Gene therapy is emerging as a disease-modifying strategy targeting dopamine restoration, neurotrophic support, and pathogenic mutation correction.
- Current approaches include viral and non-viral platforms for dopamine biosynthesis, neurotrophic factor delivery, and mutation correction (e.g., GBA1, LRRK2, PINK1).
- Clinical trials focus on dopamine synthesis (AAV2 AADC, ProSavin/AXO Lenti PD), neurotrophic factors (AAV2 GDNF, AAV2 NRTN), and pathogenic variants (AAV9 GBA1/PR001, LRRK2 RNAi, CRISPR/PINK1).
- Challenges include vector biodistribution, immune responses, retrograde transport limitations, and surgical infrastructure needs.
- Future directions involve engineered capsids, delivery optimization, and biomarkers for precision interventions.