An update on the treatment of Parkinson's disease

Although levodopa remains the most effective symptomatic drug for Parkinson's disease (PD), its use is limited by the emergence of motor fluctuations and dyskinesias, particularly in young-onset patients. Dopamine agonists, catechol-O-methyltransferase inhibitors and other anti-parkinsonian drugs have been found to diminish or prevent these complications and possibly to exert disease-modifying effects. The finding that the subthalamic nucleus (STN) and the globus pallidum internus (GPi) are abnormally active in PD has led to effective surgical treatments designed to improve patients' quality of life. The relative benefits of targeting STN or GPi with high-frequency stimulation are still being debated. Experimental therapeutics of PD include novel delivery systems, anti-apoptotic strategies and implantation of genetically engineered cells, and stem cells. Despite encouraging results from early pre-clinical and clinical studies, trials of human fetal grafts and intraventricular and intraparenchymal infusion of glial cell-line-derived neurotrophic factor have not shown clinically meaningful benefits. Future therapeutic strategies should focus not only on ameliorating the symptoms of PD, but also on neuroprotective or neurorescue therapies that can favorably modify the natural course of the disease and slow the progression of both motor and nonmotor manifestations of PD.