New iPS Stem Cells for PD: What Does it Mean?

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.

Selected References:

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 Global Administrator

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. 

April 2015
What to tell Parkinson’s patients about diet and taking statin drugs

March 2015
Everything a Parkinson’s Disease Patient Needs to Know About the New Dopamine Pump

February 2015
Tips for Parkinson’s Disease Patients Switching from Sinemet or Madopar to Rytary (IPX066)

January 2015
More Evidence Linking Gut Bacteria to Parkinson’s Disease: A Guide for Patients

December 2014
Two New Therapies for Parkinson’s Disease Patients to get Excited About: Vaccines and Monoclonal Antibodies

November 2014
The Importance of a Monitoring Strategy When Prescribing Dopamine Agonists: Lessons from the National Parkinson Foundation Data

October 2014
Is Midlife Migraine Related to Late Life Parkinson’s Disease?

September 2014
Deep Brain Stimulation for Parkinson’s Disease: NPF Congratulates Mahlon DeLong and Alim-Louis Benabid and Looks to a Bright Future in Human Neural-Network Modulation

August 2014
Everything You Need to Know About Medical Marijuana and Parkinson’s Disease

July 2014
The End for Levodopa Phobia: New Study Shows Sinemet is a Safe Initial Therapy for Treatment of Parkinson's Disease

June 2014
Is light therapy a potential treatment modality in Parkinson’s disease?

May 2014
How does the most common genetic cause of Parkinson’s Disease (LRRK2) cause Parkinson’s disease and could it be used to help develop a better therapy?

April 2014
An Update on DAT Scanning for Parkinson’s Disease Diagnosis

March 2014
Could Northera (Droxidopa) Be an Alternative Treatment for Low Blood Pressure and Passing Out Symptoms?

February 2014
The Dream of a Pill Free Existence and the Continuous Dopaminergic Pump for the Treatment of Parkinson's Disease

January 2014
Should I take Inosine to Raise my Uric Acid Levels and Treat my Parkinson’s Disease?

December 2013
Could Fungus and Mold be an Important Contributor to Parkinson’s Disease?

November 2013
Pimavanserin and the Hope for a Better Drug for Hallucinations and Psychosis in Parkinson’s Disease

October 2013
Halting of the Creatine Study

September 2013
The Importance of Identifying and Treating Caregiver Strain

August 2013
Putting Parkinson’s Disease Information into the Palm of Your Hand: Parkinson’s Enters the Smartphon

July 2013
What Parkinson’s Disease Patients Need to Know about H. Pylori Gastrointestinal Infections

June 2013
A2A Receptor Antagonists and Parkinson’s Disease Treatment

May 2013
Another Setback for Trophic Factor Treatment in Parkinson's Disease

April 2013
IPX066 and What Patients Really Want in New Carbidopa/Levodopa (Sinemet) Formulations

March 2013
The Weather Forecast for Parkinson’s Disease Calls for Worldwide Economic Storm

February 2013
Defeating the Barriers to Implementing Exercise Regimens in Parkinson’s Disease Patients

January 2013
When should you start medication therapy for Parkinson’s disease?

December 2012
Neurologist Care Reduces Hospitalizations in Parkinson's Disease

November 2012
A Victory in Court for Parkinson's Disease Patients who Require Ongoing Rehabilitative Therapies

October 2012
Given the recent FDA announcement about Mirapex (pramipexole), should I be worried about dopamine agonists?

September 2012
What about the new Parkinson’s Disease Vaccine? What should I know?

August 2012
Caffeine as a Potential Treatment for Parkinson’s Disease

July 2012
Time to Consider GPi DBS for Parkinson’s Disease: A Shift in the Practice of Patient Selection for DBS

June 2012
A New Treatment for Parkinson’s Disease-Related Constipation

May 2012
Too Many Pills: Improving Delivery Systems for Parkinson’s Disease Drugs

April 2012
Measuring Quality and Assessing Depression in Parkinson's Disease

March 2012
Watch out for Unexpected Obstacles if You Use a Cueing Strategy to Break Freezing of Gait in Parkinson’s Disease

February 2012
Pill Color, Generic Medications and Insurance Issues: Important Medication-Related Tips for the Parkinson’s Disease Patient

January 2012
Are Blood Tests for Parkinson’s Disease on the Horizon?

December 2011
Placing Stem Cells in Animal Models of Parkinson’s Disease: Another Important Step

November 2011
Important News for the Parkinson’s Disease Community: More Evidence that Sinemet and Madopar are Not Toxic and do Not Accelerate Disease Progression

October 2011
The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team

September 2011
Scientists say Research on Brain Proteins Involved in Parkinson’s Disease is “Shaping” Up

August 2011
Who Actually Takes Care of Most of the Parkinson’s Patients Worldwide: The Need for Education and the Parkinson’s Toolkit

July 2011
If you are Dizzy or Passing Out, it could be Your Parkinson’s Disease or Parkinson’s Disease Medications

June 2011
How Will Group Visits for Parkinson’s Disease Fit into the Future of Parkinson’s Disease Care?

May 2011
Why Patients Should be Wary of Chelation Therapy for Parkinson’s Disease

April 2011
Opening the Door to Gene Therapy in Parkinson’s Disease: The Need for Refinement of the Technology and Approach

March 2011
Does it Matter if I Can’t Get Brand Sinemet?

February 2011
Should I get a DaTscan or PET scan to confirm my diagnosis of Parkinson’s disease?

January 2011
A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease

December 2010
Environmental Risks for PD: Manganese, Welding, Mining, and Parkinsonism

November 2010
Calling for the FDA to Revise the Eight Sinemet a Day Rule

October 2010
Dry Cleaning Solvents and Potential Environmental Risks for Developing Parkinson’s Disease

September 2010
Maintaining the Balance: Why Parkinson’s Disease Patients Need to Understand Drug Recalls, Withdrawals, and Safety Alerts

August 2010
Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research

July 2010
Poor Medication Management of Parkinson's Disease During Hospital Admissions: Patients and Families Can Improve Their Hospital-Based Management

June 2010
Why Are Patches and Continuous Release Technology a Big Deal to Parkinson's?

May 2010
Is the PD SURG Trial Another Surge Forward for DBS Therapy?

April 2010
Cycling in PD in Those Who Can’t Walk: Is it Possible?

March 2010
New iPS Stem Cells for PD: What Does it Mean?

February 2010
Time for Comprehensive Care Networks for PD

January 2010
Is Parkinson's Disease a Prion Disease?

December 2009
Parkinson's Disease Linked to Gaucher's Disease

November 2009
Brain Cells Keep Time Stamps: Implications for Parkinson's Disease Therapies

October 2009
Is it Safe to Have an MRI with a DBS in Place?

September 2009
Take Care of Your Bones as They Are Affected in Parkinson's Disease (Even in Men)

August 2009
Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?

July 2009
Glutathione Fails to Demonstrate Significant Improvement in PD Symptoms

June 2009
Keeping an Eye on Trials Important to the Parkinson's Disease Patient

May 2009
Increased Risk of Melanoma in Parkinson's Disease

April 2009
Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients

March 2009
Pesticides and Environmental Exposure in Parkinson's disease: Should We Stay Away From the Stink Truck?

February 2009
Is Exercise Effective Treatment and Protection Against PD?

January 2009
Why are Transplant Trials Struggling to Succeed in the Treatment of PD?

December 2008
Are Monoamine Oxidase Inhibitors Disease Modifying or Neuroprotective in PD?

November 2008
Update on Gene Therapy for Parkinson's Disease

Currently: 0 (0 ratings)


Each month, we will feature a new column by NPF's National Medical Director, Dr. Michael Okun, on the latest developments in Parkinson's disease research. Read the latest "What's Hot in PD?" below.

Subscribe to this blog