WHERE DO WE STAND ON NEUROPROTECTION - WHERE DO WE GO FROM HERE

Neuroprotective therapies are interventions that produce enduring bene fits by favorably influencing underlying etiology or pathogenesis of n eurodegenerative disorders. Neuroprotection remains an unachieved goal of experimental therapeutics. A variety of pathogenetic mechanisms an d propagating factors have been implicated in the emergence and progre ssion 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 t o enhanced dopaminergic activity may not be suitable for distinguishin g symptomatic from neuroprotective effects. Inferences supporting neur oprotective effects in clinical trials would be strengthened by attent ion to unmet therapeutic needs or relevant clinical end points that ar e not currently amenable to dopaminergic treatments. Progressive postu ral instability and intellectual impairment (dementia) represent two m ajor unmet therapeutic needs in PD that are worthy outcomes in therape utic trials. Imaging tools such as [F-18]-dopa PET and [I-123] B-CIT S PECT 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 cent ral role in development of neuroprotective therapy for PD.