Clinical trials for neuroprotection in Parkinson's disease: overcoming angst and futility?

PURPOSE OF REVIEW: To summarize recently published results of neuroprotection trials for Parkinson's disease, and discuss them in the context of evolving concepts in clinical study design and animal models. RECENT
FINDINGS: Despite compelling preclinical evidence from laboratory models suggesting potential neuroprotective benefits, the antioxidant, antiapoptotic, antiexcitotoxic, immunomodulatory and neurotrophic agents studied to date have not shown clear benefit in human studies. The futility study design, an alternative approach focused on efficiently excluding less promising compounds, has been adopted recently to investigate four candidate neuroprotectants. A delayed-start trial design has also been introduced in a study of the monoamine oxidase inhibitor rasagiline, demonstrating a possible neuroprotective effect as well as its clear symptomatic benefit. In parallel with these clinical innovations, preclinical research initiatives are identifying new animal models that more closely resemble the clinical course and pathology of Parkinson's disease.
SUMMARY: Angst over disappointing results of neuroprotection trials in Parkinson's disease has engendered efforts to refine animal models at one end of the therapeutics pipeline, and to optimize clinical trial design at the other. Building on new insights into the genetics, epidemiology and pathogenesis of Parkinson's disease, these recent improvements in 'translational infrastructure' will enhance the prospects of achieving the critical goal of slowing the progression of disability.