By: Michael S. Okun, M.D., National Medical Director, National Parkinson Foundation & Vinata Vedam-Mai, Ph.D.,University of Florida, Departments of Neurology and Neurosurgery
You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Center for Movement Disorders & Neurorestoration.
One of the most recent and remarkable scientific developments has been the ability of scientists to manipulate somatic cells (e.g. skin cells) in such a way that they can be re-programmed to become pluripotent (they gain the ability to form multiple different cell types in the body). This ability is the result of inducing expression of several transcription factors (transcription factors encode the genetic maps in any individual person) and this induction results in the generation of what have been referred to as induced pluripotent stem (iPS) cells. In initial experiments, a combination of chemicals Oct4, Sox2, Klf4 and Myc were used to induce a transition of fibroblasts (e.g. parts of skin cells) into stable and self-renewing cells that very closely resembled embryonic stem cells (ES). Subsequently, this type of reprogramming has been demonstrated in a wide range of cell types.
Several techniques have been employed to achieve reprogramming of cells from various body tissues (somatic cells). These methods include nuclear transfer, cell fusion of somatic cells with ES cells, explantation of somatic cells in culture (from a dish in the lab), and the transduction of somatic cells with defined factors/chemicals. The exact molecular mechanism of this reprogramming however, is still uncertain. It will be necessary in the future to unlock the mystery behind why this reprogramming works, in order for us to understand why the process proceeds so slowly (often over a period of several weeks), and why only a small proportion of the infected fibroblasts (usually skin cells) achieve iPS cell status.
iPS cell possibilities precipitate the question that is on all Parkinson’s disease patient’s minds: would it be possible through cell reprogramming to generate tailor made cells as neurotherapeutics? Recent studies have shown the therapeutic application for the transplantation of iPS derived dopamine neurons (brain cells) in a rat model of Parkinson’s disease. In these studies it was shown that dopamine neurons could be functionally integrated into the adult rat model of Parkinson’s disease, and that this could lead to an improvement in the clinical symptoms of the disease. Similar experiments were also performed on hemophilia A mice (iPS derived endothelial cells into liver cells) and this also resulted in disease improvement (hemophilia is a blood disease). Hence, iPS cell-based strategies could become very important in the future treatment of Parkinson’s disease.
Even though more work will be required before the generation of clinically applicable iPS cells, drug screening and disease modeling will be two potentially immediately useable applications for this technology. Improvements in high throughput screening using iPS cells may allow for reductions in cost, and improvements in safety of drug screening (identifying new drugs to treat PD). Additionally the techniques may help us to understand the underlying pathophysiology of the disease.
There will be major challenges in the clinical implementation of therapeutic preparations derived from iPS cells. It is absolutely critical that these preparations be free of undifferentiated cells that may have the potential to form tumors. Further, the efficient purification of populations of disease-relevant cells types will be a major challenge. Finally, and perhaps most importantly, the development of techniques for the precise delivery of iPS cells into patients, and the functional engraftment of the cells into the appropriate and complex basal ganglia motor and nonmotor circuits in Parkinson’s disease will provide the most formidable challenge. In summary, iPS cells should provide excitement for the Parkinson’s disease patient, but we should also realize that a lot of the foundations for success still remain to be constructed and to be built upon.
*The co-author of this month’s What’s Hot is Vinata Vedam-Mai who is a researcher working in the stem cell laboratory of Dr. Brent Reynolds at the University of Florida.
1. Forcing cells to change lineages. Grat, T. et al. Nature 2009. 462, 587-594.
2. Progress toward the clinical application of patient-specific pluripotent stem cells. Kiskinis, E. et al. J. Clin. Invest. 2010. 120 (1) 51-59.
3. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Jaenish, R et. al. Cell, 2008. 132, 567-582.
4. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 2009. 136 (5) 964-977.
Posted: 2/23/2010 9:22:39 AM by
Browse current and archived What's Hot in PD? articles, the National Parkinson Foundation's monthly blog for people with Parkinson's written by our National Medical Director, Dr. Michael S. Okun.
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Caffeine as a Potential Treatment for Parkinson’s Disease
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A New Treatment for Parkinson’s Disease-Related Constipation
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Pill Color, Generic Medications and Insurance Issues: Important Medication-Related Tips for the Parkinson’s Disease Patient
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Placing Stem Cells in Animal Models of Parkinson’s Disease: Another Important Step
Important News for the Parkinson’s Disease Community: More Evidence that Sinemet and Madopar are Not Toxic and do Not Accelerate Disease Progression
The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team
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Why Patients Should be Wary of Chelation Therapy for Parkinson’s Disease
Opening the Door to Gene Therapy in Parkinson’s Disease: The Need for Refinement of the Technology and Approach
Does it Matter if I Can’t Get Brand Sinemet?
Should I get a DaTscan or PET scan to confirm my diagnosis of Parkinson’s disease?
A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease
Environmental Risks for PD: Manganese, Welding, Mining, and Parkinsonism
Calling for the FDA to Revise the Eight Sinemet a Day Rule
Dry Cleaning Solvents and Potential Environmental Risks for Developing Parkinson’s Disease
Maintaining the Balance: Why Parkinson’s Disease Patients Need to Understand Drug Recalls, Withdrawals, and Safety Alerts
Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research
Poor Medication Management of Parkinson's Disease During Hospital Admissions: Patients and Families Can Improve Their Hospital-Based Management
Why Are Patches and Continuous Release Technology a Big Deal to Parkinson's?
Is the PD SURG Trial Another Surge Forward for DBS Therapy?
Cycling in PD in Those Who Can’t Walk: Is it Possible?
New iPS Stem Cells for PD: What Does it Mean?
Time for Comprehensive Care Networks for PD
Is Parkinson's Disease a Prion Disease?
Parkinson's Disease Linked to Gaucher's Disease
Brain Cells Keep Time Stamps: Implications for Parkinson's Disease Therapies
Is it Safe to Have an MRI with a DBS in Place?
Take Care of Your Bones as They Are Affected in Parkinson's Disease (Even in Men)
Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?
Glutathione Fails to Demonstrate Significant Improvement in PD Symptoms
Keeping an Eye on Trials Important to the Parkinson's Disease Patient
Increased Risk of Melanoma in Parkinson's Disease
Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients
Pesticides and Environmental Exposure in Parkinson's disease: Should We Stay Away From the Stink Truck?
Is Exercise Effective Treatment and Protection Against PD?
Why are Transplant Trials Struggling to Succeed in the Treatment of PD?
Are Monoamine Oxidase Inhibitors Disease Modifying or Neuroprotective in PD?
Update on Gene Therapy for Parkinson's Disease