Trends in Pharmacological Sciences
Neuroprotective strategies for Parkinson's disease: conceptual limits of animal models and clinical trials
Section snippets
Conceptual limits of animal models of PD and their use
Surprisingly, data resulting from the use of the above-mentioned agents in animal models of PD using what we propose to call a ‘clinically driven design’ have not been published. Such a design should ideally satisfy the following three criteria. First, the chosen animal model should recapitulate most, if not all, features of sporadic PD, including its progressiveness (all acute models are excluded, although useful for initial screening) and its pathological landmark (i.e. the replication of
Conceptual limits of clinical trials
Even using the best experimental approach, clinical trials suffer from drawbacks that cause us to doubt our ability to demonstrate soundly the protective capacity of a drug, a fact that explains why the regulatory authorities view the field with suspicion. Several human studies have investigated putative neuroprotective effects of DA receptor agonists on nigrostriatal degeneration using imaging techniques [14]. These imaging techniques assess either DA terminal function or DA transporter
Concluding remarks
Current clinical trials and animal models of PD are insufficient to assess neuroprotective properties of any tested agent. Although this is in agreement with the concept of clinical equipoise (a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial [18]), the selection of interesting agents for upcoming clinical trials should be based on the most sound, clinically driven preclinical validation. Thus, we herein
Acknowledgments
W.M. is a Marie Curie Fellow of the European Community (HPMF-2001–01300). M.H. is Chief Operating Officer and E.B. is Non-Executive Director of Motac Neuroscience, Manchester, UK.
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