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Treatment of Parkinson's Disease Through Personalized Medicine and Induced Pluripotent Stem Cells


Treatment of Parkinson's Disease Through Personalized Medicine and Induced Pluripotent Stem Cells

Theo Stoddard-Bennett et al. Cells.


Parkinson's Disease (PD) is an intractable disease resulting in localized neurodegeneration of dopaminergic neurons of the substantia nigra pars compacta. Many current therapies of PD can only address the symptoms and not the underlying neurodegeneration of PD. To better understand the pathophysiological condition, researchers continue to seek models that mirror PD's phenotypic manifestations as closely as possible. Recent advances in the field of cellular reprogramming and personalized medicine now allow for previously unattainable cell therapies and patient-specific modeling of PD using induced pluripotent stem cells (iPSCs). iPSCs can be selectively differentiated into a dopaminergic neuron fate naturally susceptible to neurodegeneration. In iPSC models, unlike other artificially-induced models, endogenous cellular machinery and transcriptional feedback are preserved, a fundamental step in accurately modeling this genetically complex disease. In addition to accurately modeling PD, iPSC lines can also be established with specific genetic risk factors to assess genetic sub-populations' differing response to treatment. iPS cell lines can then be genetically corrected and subsequently transplanted back into the patient in hopes of re-establishing function. Current techniques focus on iPSCs because they are patient-specific, thereby reducing the risk of immune rejection. The year 2018 marked history as the year that the first human trial for PD iPSC transplantation began in Japan. This form of cell therapy has shown promising results in other model organisms and is currently one of our best options in slowing or even halting the progression of PD. Here, we examine the genetic contributions that have reshaped our understanding of PD, as well as the advantages and applications of iPSCs for modeling disease and personalized therapies.

Keywords: Parkinson’s disease; alpha-synuclein; cell- and tissue-based therapy; disease modeling; dopaminergic neurons; induced pluripotent stem cells.

Conflict of interest statement

The authors declare no conflict of interest.


Figure 1
Figure 1
Clinical trials that have been or are being conducted worldwide to treat neurodegeneration using stem cells. To date, 170 clinical trials have employed mesenchymal stem cells (MSC), neural progenitor stem cells (NPC) and bone marrow-derived mononuclear cells (BM-MNC) in attempts to alleviate the neurodegeneration of Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinal cord injury (SCI) and brain ischemia (BI). The data was collected from on 21 December 2018.
Figure 2
Figure 2
The progression of pluripotent cell-based therapies within the context of Parkinson’s Disease (PD) research. Beginning in 1987, fetal ventral midbrain (VM) tissue used as the cell source for the first clinical trial using cells to treat PD. In recent years, human embryonic stem cells (hESCs) are being utilized in a number of clinical trials involving neurodegeneration. Use of hESCs has shown special promise in spinal cord injury (SCI), age-related macular degeneration (AMD) as well as cell damage to the heart. In the summer of 2018, clinicians are beginning to undertake the first human trial using induced pluripotent stem cells (iPSCs) as a cell source to treat PD [57]. This trial will follow seven patients over the course of two years. The outcomes of these trials are detailed in the text.
Figure 3
Figure 3
iPSC transplantation. First, fibroblasts are obtained from a patient afflicted with familial PD. Researchers express major reprogramming transcription factors to establish a mutant iPSC line. Using ZNF/TALEN or CRISPR/Cas9 technology, the significant mutation is corrected and then the line is differentiated into mature or progenitor DA neurons in xeno-free conditions. After sufficient quality assurance, the differentiated cells can then be used for clinical trials.

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