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Drug discovery in Parkinson's disease: update and developments in the use of cellular models

Authors Skibinski G, Finkbeiner S

Published 30 June 2011 Volume 2011:2 Pages 15—25


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Gaia Skibinski, Steven Finkbeiner
Gladstone Institute of Neurological Disease, San Francisco, CA, USA

Abstract: Parkinson's disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons within the substantia nigra. Dopamine replacement drugs remain the most effective treatment for Parkinson's disease but only provide temporary symptomatic relief. New therapies are urgently needed, but the search for a disease-modifying treatment and a definitive understanding of the underlying mechanisms of Parkinson's disease has been limited by the lack of physiologically relevant models that recapitulate the disease phenotype. The use of immortalized cell lines as in vitro model systems for drug discovery has met with limited success, because efficacy and safety too often fail to translate successfully in human clinical trials. Drug discoverers are shifting their focus to more physiologically relevant cellular models, including primary neurons and stem cells. The recent discovery of induced pluripotent stem cell technology presents an exciting opportunity to derive human dopaminergic neurons from patients with sporadic and familial forms of Parkinson's disease. We anticipate that these human dopaminergic models will recapitulate key features of the Parkinson's disease phenotype. In parallel, high-content screening platforms, which extract information on multiple cellular features within individual neurons, provide a network-based approach that can resolve temporal and spatial relationships underlying mechanisms of neurodegeneration and drug perturbations. These emerging technologies have the potential to establish highly predictive cellular models that could bring about a desperately needed revolution in Parkinson's disease drug discovery.

Keywords: Parkinson's disease, cellular models, drug delivery

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