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Designer receptors: therapeutic adjuncts to cell replacement therapy in Parkinson’s disease
Elena M. Vazey, Gary Aston-Jones
Elena M. Vazey, Gary Aston-Jones
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Designer receptors: therapeutic adjuncts to cell replacement therapy in Parkinson’s disease

Abstract

Cell replacement for restoring neuronal populations in Parkinson’s disease has been demonstrated as a potential therapeutic strategy over several decades of studies; however, a number of issues regarding sources of replacement neurons and optimization of therapeutic efficacy in vivo have hampered clinical implementation. In this issue of the JCI, Dell’Anno and colleagues evaluated the use of induced dopaminergic (iDA) neurons that were generated by direct fibroblast reprogramming for transplantation and demonstrated that postmitotic iDA neurons stably and functionally integrate into host striatum to produce motor improvements in 6-OHDA rats, a Parkinson’s disease model. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs) in iDA grafts to noninvasively increase dopamine release from grafted neurons, the authors were able to remotely control transplanted neurons and enhance therapeutic efficacy. This initial proof-of-concept study is the first application of DREADD technology to treat neurodegenerative dysfunction, and by using DREADDs as an adjunct to iDA cell therapy, it presents a novel strategy to overcome some current caveats of cell replacement therapy.

Authors

Elena M. Vazey, Gary Aston-Jones

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