Replacing the Cells Lost in Parkinson Disease

Replacing the Cells Lost in Parkinson Disease Wednesday, 05 December 2007 Parkinson disease (PD) is caused by the progressive degeneration of brain cells known as dopamine (DA) cells. Replacing these cells is considered a promising therapeutic strategy. Although DA cell–replacement therapy by transplantation of human foetal mesencephalic tissue has shown promise in clinical trials, limited tissue availability means that other sources of these cells are needed. Now, Ernest Arenas and colleagues at the Karolinska Institute, together with Olle Lindvall’s group at the Wallenberg Neuroscience Center in Lund, Sweden, have identified a new source for DA cells that provided marked benefit when transplanted into mice with a PD-like disease. In the study, DA cells were derived from ventral midbrain (VM) neural stem cells/progenitors by culturing them in the presence of a number of growth factors — FGF2, sonic hedgehog, and FGF8 — and engineering them by transfection to express Wnt5a. This protocol generated 10-fold more DA cells than did conventional FGF2 treatment. These cells exhibited the transcriptional and biochemical profiles and intrinsic electrophysiological properties of midbrain DA cells. Further analysis revealed that these cells initiated substantial cellular and functional recovery when transplanted into mice with PD-like disease. Importantly, the mice did not develop tumours, a potential risk that has precluded the clinical development of embryonic stem cells as a source of DA cells. These data led the authors to suggest that Wnt5a-treated neural stem cells might be an efficient and safe source of DA cells for the treatment of individuals with PD. Reference: Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice J Clin Invest. Published online 2007 December 3. doi: 10.1172/JCI32273. ......... ZenMaster

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