Limitations of current Parkinson's disease therapy

Levodopa and other dopaminergic medications drastically improve the motor symptoms and quality of life of patients with Parkinson's disease in the early stages of the disease. However, once the honeymoon period has waned, usually after a few years of dopaminergic therapy, patients become progressively more disabled despite an ever more complex combination of available antiparkinsonian treatments. Sooner or later, they suffer from dopa-resistant motor symptoms (speech impairment, abnormal posture, gait and balance problems), dopa-resistant nonmotor signs (autonomic dysfunction, mood and cognitive impairment, sleep problems, pain) and/or drug-related side effects (especially psychosis, motor fluctuations, and dyskinesias). Therefore, the current antiparkinsonian therapy cannot be considered as ideal with regard to both efficacy and safety.