This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Restorative approaches for Parkinson s disease (PD) include the replacement of dopamine (DA) neurons by trans-planting fetal ventral midbrain (VM). Fetal VM is an unreliable cell source with many associated technical problems. Embryonic stem (ES) cells offer a realistic alternative to fetal cells for cell-based replacement therapies since they are renewable and can be controlled for cell types and reproducibility. We have derived DA neurons from primate and human embryonic ES cell sources. In this project, we will determine the therapeutic potential of DA neurons derived from ES cells by transplantation into MPTP-lesioned parkinsonian primates. First we will examine the capacity of transplanted DA neurons derived from primate and human ES cells to improve parkinsonian signs, in comparison to standard L-DOPA therapy. Detailed motor behavioral evaluation and functional neuroimaging using 18F-F-DOPA, 11C-CFT PET and MRI will be combined and correlated with histological analyses. This project is necessary to determine the growth, functional benefits and safety of ES cell derived DA neurons in a primate model of PD in order to translate the experimental hypothesis into a clinically relevant procedure. The biomedical and clinical work also involves establishing novel technology to grow, maintain and transfer cells (rather than drugs) in a safe and effective manner.
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