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- W2906201488 abstract "Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Foetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on-going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (a) they often lack synucleinopathy, and (b) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post-mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α-synuclein mechanisms. Furthermore, these patients are usually younger, slow progressing and typically do not suffer from complex non-nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild-type PARKIN expression to re-innervate the striatum. The focal nature of PARKIN-mediated neurodegeneration and lack of active synucleinopathy in most young-onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α-synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy." @default.
- W2906201488 created "2019-01-01" @default.
- W2906201488 creator A5001035756 @default.
- W2906201488 creator A5008886339 @default.
- W2906201488 creator A5014253845 @default.
- W2906201488 creator A5053039871 @default.
- W2906201488 creator A5057119874 @default.
- W2906201488 creator A5062846077 @default.
- W2906201488 creator A5066316533 @default.
- W2906201488 creator A5084528692 @default.
- W2906201488 date "2019-01-23" @default.
- W2906201488 modified "2023-09-26" @default.
- W2906201488 title "Are <i>PARKIN</i> patients ideal candidates for dopaminergic cell replacement therapies?" @default.
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