Although still a disorder of unknown etiology, Parkinson's disease (PD) has provided a number of clues that have led to clinical trials of neuroprotection. For example, defects in mitochondrial metabolism and evidence for oxidative stress in PD have fostered therapeutic interventions aimed at slowing disease progression. More than a dozen compounds already have been tested in PD for disease modification, and others are in planning stages for clinical trials. The challenge is to find a highly

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... ective therapy halting disease progression (beyond the relatively modest clinical effect exemplified by recent findings with coenzyme Q-10 treatment administered at 1200 mg=day). Clinical exam-based ratings and disability assessments still serve at providing the primary evidence of efficacy. However, with surrogate biomarkers such as radiotracer neuroimaging of the dopaminergic system, the pace of clinical investigation can be increased. Recent years have seen the utilization of more sensitive study methods in PD neuroprotection research, such as staggered wash-in, 2 Â 2 factorial, and "futility" trial designs. The results of several ongoing PD neuroprotection trials are planned for release in the near future. Correspondence: P. A. LeWitt, MD,