Disease-Modifying Strategies in Parkinson's Disease

Abstract

The course of Parkinson's disease (PD) after typical motor symptomsare apparent is one of gradual worsening over a decade ormore, corresponding to ongoing neuronal loss affecting cellsin the pigmented nuclei of the brainstem, particularly in thesubstantia nigra. There is a preclinical phase of uncertain duration(1), during which loss of dopaminergic neurons and otherneuropathologic changes progress until the threshold for clinicalmotor symptoms is reached. Recently, the diagnostic criteriaof PD have been challenged and the Movement Disorders Societyhas settled a Task Force to establish a new set of diagnosticcriteria (2). The estimated neuron loss by the time of diagnosisis about 60% (3). PD progression ultimately leads to importantdisability, handicap, and death (4). Despite current best standardof care, mortality among PD patients is still higher thanthe general population one (5). Given this course, there is agrowing interest in developing interventions that can changeit for the better. It is believed that to obtain an important clinicalimpact on the natural course of disease, the interventionshould have a long-lasting effect that goes beyond the immediatecontrol of signs and symptoms. This is the essence of thedisease-modifying concept.