l-DOPA-induced dyskinesia in Parkinson's disease: a drug discovery perspective

l-DOPA-induced dyskinesia is a debilitating, treatment-limiting adverse effect that eventually occurs in the majority of Parkinson's disease patients. This review describes the strategy of biological testing, focusing on in vivo proof-of-concept animal models. We distinguish between symptomatic efficacy markers in predictive preclinical in vivo models and confounding factors that eventually produce false positive results. Clinical studies and predicted efficacy from preclinical studies are recapitulated and insights into the attempt to bridge preclinical and clinical studies are given. Furthermore, the mode of action that is to be involved in emerging therapy against l-DOPA-induced dyskinesia is reviewed.