CAN THE NEUROPROTECTIVE EFFICACY OF AN AGENT EVER BE CONCLUSIVELY PROVEN

Clinical examination of Parkinson's disease is typically hindered by t he influence of medication upon scaled tests and the heterogeneity of disease progression. Similarly, these problems, together with the symp tomatic effects of most drugs, can obscure measurement of the neuropro tective efficacy of an agent. Diagnosis and assessment could be improv ed by the use of objective functional imaging techniques, such as F-18 -L-3,4-dihydroxyphenylalanine (F-18-L-DOPA) positron emission tomograp hy (PET), that provide a measure of Parkinson's disease, independent o f medication or disease factors, which can be correlated with traditio nal scales. PET analyses must be sensitive, reproducible and assess ar eas of the brain predominantly affected in Parkinson's disease. The te chnique is sensitive enough to indicate that Parkinson's disease sympt oms start after a 25% decrease in the normal putamen dopaminergic acti vity, in contrast to the >50% decrease previously supposed. The reprod ucibility of the technique allows construction of a matrix for a clini cal trial size to achieve a measure of the neuroprotective efficacy of an agent, using F-18-L-DOPA-PET as an assessment tool. This will allo w appropriate trials to be designed to account for the inherent hetero geneity of Parkinson's disease.