Where do we stand on neuroprotection? Where do we go from here?

Neuroprotective therapies are interventions that produce enduring benefits by favorably influencing underlying etiology or pathogenesis of neurodegenerative disorders. Neuroprotection remains an unachieved goal of experimental therapeutics. A variety of pathogenetic mechanisms and propagating factors have been implicated in the emergence and progression of Parkinson's disease (PD). Antioxidative strategies have been the focus of neuroprotective trials for PD, but interpretation of the outcomes has been controversial. Traditional end points that respond to enhanced dopaminergic activity may not be suitable for distinguishing symptomatic from neuroprotective effects. Inferences supporting neuroprotective effects in clinical trials would be strengthened by attention to unmet therapeutic needs or relevant clinical end points that are not currently amenable to dopaminergic treatments. Progressive postural instability and intellectual impairment (dementia) represent two major unmet therapeutic needs in PD that are worthy outcomes in therapeutic trials. Imaging tools such as [F-18]-dopa PET and [I-123] B-CIT SPECT may provide valid and reliable biologic markers of nigrostriatal degeneration. Controlled clinical trials focused on unmet therapeutic needs, and involving valid biologic markers is expected to play a central role in development of neuroprotective therapy for PD.