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Abstract

Cell-based therapies that involve transplantation into the striatum of dopaminergic cells have attracted considerable interest as possible treatments for Parkinson's disease (PD). However, all double-blind, sham-controlled, studies have failed to meet their primary endpoints, and transplantation of dopamine cells derived from the fetal mesencephalon is associated with a potentially disabling form of dyskinesia that persists even after withdrawal of levodopa (off-medication dyskinesia). In addition, disability in advanced patients primarily results from features such as gait dysfunction, freezing, falling, and dementia, which are likely due to nondopaminergic pathology. These features are not adequately controlled with dopaminergic therapies and are thus unlikely to respond to dopaminergic grafts. More recently, implanted dopamine neurons have been found to contain Lewy bodies, suggesting that they are dysfunctional and may have been affected by the PD pathological process. Collectively, these findings do not bode well for the short-term future of cell-based dopaminergic therapies in PD. Ann Neurol 2009;66:591–596