Parkinson's disease (PD) results from degeneration of midbrain dopamine (DA) neurons and can be effectively treated with L-dopa in the initial phase. However, DA supplementation does not halt the DA neuron degeneration process, nor does it correct the loss of DA neurons. Consequently, PD patients almost invariably lose responsiveness to L-dopa treatment over time. Transplantation of human fetal mesencephalic tissues to replace the lost DA neurons has shown efficacy in alleviating symptoms of some PD patients. This therapy, however, depends on collection of tissues from multiple fetuses of particular ages for a single patient, which makes it impractical for general application and is ethically problematic. This proposal explores the possibility of future personalized cell therapy for PD using a non-human primate model. We will derive safe and functional DA neurons from the skin tissue of individual Parkinsonian rhesus monkeys through generation of induced pluripotent stem cells (iPSCs) that are free of virus and transgenes and using our newly developed strategy for midbrain DA neuron differentiation. We will then label the cell genetically and transplant the midbrain DA neurons back to the monkey from which the cells are derived, and assess whether the DA neurons survive and contribute to therapy in a short term and whether the therapeutic outcome is sustained over a long term (2-3 years). Results from this study will determine the safety and efficacy of autologous stem cell therapy for PD in primates, thus setting up a foundation for future clinical trials using reprogrammed human cells.

Public Health Relevance

This study will derive dopamine nerve cells from monkey's skin tissue and transplant the nerve cells back to the Parkinson's monkey to determine if such autologous cell therapy will lead to long lasting improvement of movement deficits. This study mimics and sets up a foundation for future personalized therapy using reprogrammed human cells.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Sutherland, Margaret L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Fathi, Ali; Mirzaei, Mehdi; Dolatyar, Banafsheh et al. (2018) Discovery of Novel Cell Surface Markers for Purification of Embryonic Dopamine Progenitors for Transplantation in Parkinson's Disease Animal Models. Mol Cell Proteomics 17:1670-1684
Vermilyea, Scott C; Emborg, Marina E (2018) The role of nonhuman primate models in the development of cell-based therapies for Parkinson's disease. J Neural Transm (Vienna) 125:365-384
Jones, Jeffrey R; Kong, Linghai; Hanna 4th, Michael G et al. (2018) Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes. Cell Rep 25:947-958.e4
Vermilyea, Scott C; Lu, Jianfeng; Olsen, Miles et al. (2017) Real-Time Intraoperative MRI Intracerebral Delivery of Induced Pluripotent Stem Cell-Derived Neurons. Cell Transplant 26:613-624
Qian, Kun; Huang, Hailong; Peterson, Andrew et al. (2017) Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo. Stem Cell Reports 8:843-855
Vermilyea, Scott C; Guthrie, Scott; Meyer, Michael et al. (2017) Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Adult Common Marmoset Fibroblasts. Stem Cells Dev 26:1225-1235
Tao, Yunlong; Zhang, Su-Chun (2016) Neural Subtype Specification from Human Pluripotent Stem Cells. Cell Stem Cell 19:573-586
Lu, Jianfeng; Zhong, Xuefei; Liu, Huisheng et al. (2016) Generation of serotonin neurons from human pluripotent stem cells. Nat Biotechnol 34:89-94
Chen, Yuejun; Xiong, Man; Dong, Yi et al. (2016) Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson's Disease. Cell Stem Cell 18:817-26
Jones, Jeffrey R; Zhang, Su-Chun (2016) Engineering human cells and tissues through pluripotent stem cells. Curr Opin Biotechnol 40:133-138

Showing the most recent 10 out of 21 publications