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Two studies look at the use of iPS cell-derived neurons and Parkinson’s disease. In one of the studies, published in Nature, researchers used stem cell therapy to attempt to restore nerve function in a monkey model of Parkinson’s disease. In the other, published in Nature Communications, researchers have looked at methods of improving survival of transplanted iPS cell-derived neurons by matching the proteins of the major histocompatibility complex of the recipient in addition to use of immunosuppressive drugs.
Prof David Dexter, Deputy Research Director, Parkinson’s UK, said:
“In this first ground breaking study by Kikuchi et al*, completely new dopamine producing brain cells were created from stem cells (that had previously been created from human cells) and were successfully transplanted into a primate model of Parkinson’s.
“Not only did the new cells survive, and were found in later dissections, but they also integrated with the existing neuronal network – functioning like normal dopamine-producing brain cells and allowing gradually improved movement over a twelve-month period.
“In the primate model, these new transplanted cells effectively replaced those that are typically lost within the brains of people affected by Parkinson’s – showing very promising results for transplantation as a possible treatment for the condition.
“Should human cell transplantation become a future therapy, one of the key considerations will be to try and match the donor and the recipient to avoid an immune response that could kill the newly transplanted cells.
“To overcome the issue of transplant rejection, a second study by Morizane et al‡ successfully used the same principles of matching for organ donation to match primate brain cells to corresponding primate immune systems for the first time.
“Following this success, the researchers propose that a bank of stem cells for human transplantation could be created from just 150 donors, which would supply stem cells that could be matched to 93% of the UK population.
“Both of these studies represent an important development in the field of transplantation as a potential treatment for Parkinson’s. Current medication only serves to mask the symptoms of the condition, but makes no changes to the brain cells themselves. These studies show that, should brain cell transplantation become a viable therapy, it has the potential to reverse Parkinson’s by replacing the dopamine cells that have been lost – a groundbreaking feat.
“Although this is promising quality research, and the conclusions are backed up by solid data that comes from a variety of sources, including behavioural, brain scans and histological analysis, there are still major challenges ahead.
“We need to understand if these new transplanted cells would succumb to the same fate as the original cells that had previously died. There are also other types of brain cells that are affected by Parkinson’s and additional work must be done to tackle the symptoms of the condition that are not caused by a lack of dopamine.”
Dr Tilo Kunath, Parkinson’s UK Senior Research Fellow at the MRC Centre for Regenerative Medicine, University of Edinburgh:
“This is extremely promising research demonstrating that a safe and highly effective cell therapy for Parkinson’s can be produced in the lab. Such a therapy has the potential to reverse the symptoms of Parkinson’s in patients by restoring their dopamine-producing neurons. The next stage will be to test these therapies in a first-in-human clinical trial.
“As a side-note, the fact that the researchers have used induced Pluripotent Stem Cells (iPSCs) instead of human embryonic stem cells (hESCs) means that this therapy can be used in any country world-wide. Some countries, such as Ireland and most of South America, have banned the use of hESCs as a therapy.”
“In the second paper‡, researchers have investigated whether tissue type is important for the success of stem cell therapies in Parkinson’s disease. Tissue type is crucial for the success of organ transplants and skin grafts. If both the donor and recipient do not have matching tissue type, the recipient’s immune system will reject the transplanted tissue. However tissue type is complex and even if there is a good match, patients may be required to take immunosuppressive medication.
“The study found that immunosuppressive medication can improve the success rates of stem cell therapies in Parkinson’s disease. Their work implies that tissue matched therapies would require lower doses of the drug and for less time, which would have obvious benefits for patients.”
Prof Tom Foltynie, Consultant Neurologist and Professor of Neurology, National Hospital for Neurology & Neurosurgery, said:
“This work provides further reassurance that dopaminergic cells derived from induced pluripotent stem (iPS) cells from either healthy individuals or PD patients can survive and function long term post transplantation. Most importantly, the team found no evidence for tumour development, at least until the two year time point. The authors also identified potential factors that potentially predict which cell lines will survive and function best, which can be used to reduce the unpredictable variability that has been associated with previous fetal cell transplantation in Parkinson’s disease patients. The animal model they used was standard, however is a static model of Parkinson’s disease rather than the progressively degenerative situation that is seen in humans with Parkinson’s disease.
“As such there will be concerns about how transplants might fare in the long term in humans with Parkinson’s disease, which was also the case for the previous fetal cell trials (although long term improvements in movement have been previously reported in two patients who had fetal cell transplants in the 1990s). Overall the results they report in the short term are encouraging, and provide some reassurance that these cells can function as sources of dopamine to address those movement symptoms of Parkinson’s disease that relate to dopamine loss. No-one expects that transplants will address the non-dopamine, non-movement aspects of Parkinson’s disease such as dementia and falls which ultimately emerge with very long-term follow up.
“However by conducting this research, the authors have confronted most of the major issues associated with the development of a cell therapy for Parkinson’s disease- i.e. its safety, the main factors predictive of efficacy as well as the availability of adequate tissue. These data substantially reduce many of the previous uncertainties surrounding the development of iPS derived dopamine cell grafts as a therapy for patients with Parkinson’s disease.”
Prof David Dexter, Deputy Research Director, Parkinson’s UK, said:
“In this first ground breaking study by Kikuchi et al*, completely new dopamine producing brain cells were created from stem cells (that had previously been created from human cells) and were successfully transplanted into a primate model of Parkinson’s.
“Not only did the new cells survive, and were found in later dissections, but they also integrated with the existing neuronal network – functioning like normal dopamine-producing brain cells and allowing gradually improved movement over a twelve-month period.
“In the primate model, these new transplanted cells effectively replaced those that are typically lost within the brains of people affected by Parkinson’s – showing very promising results for transplantation as a possible treatment for the condition.
“Should human cell transplantation become a future therapy, one of the key considerations will be to try and match the donor and the recipient to avoid an immune response that could kill the newly transplanted cells.
“To overcome the issue of transplant rejection, a second study by Morizane et al‡ successfully used the same principles of matching for organ donation to match primate brain cells to corresponding primate immune systems for the first time.
“Following this success, the researchers propose that a bank of stem cells for human transplantation could be created from just 150 donors, which would supply stem cells that could be matched to 93% of the UK population.
“Both of these studies represent an important development in the field of transplantation as a potential treatment for Parkinson’s. Current medication only serves to mask the symptoms of the condition, but makes no changes to the brain cells themselves. These studies show that, should brain cell transplantation become a viable therapy, it has the potential to reverse Parkinson’s by replacing the dopamine cells that have been lost – a groundbreaking feat.
“Although this is promising quality research, and the conclusions are backed up by solid data that comes from a variety of sources, including behavioural, brain scans and histological analysis, there are still major challenges ahead.
“We need to understand if these new transplanted cells would succumb to the same fate as the original cells that had previously died. There are also other types of brain cells that are affected by Parkinson’s and additional work must be done to tackle the symptoms of the condition that are not caused by a lack of dopamine.”
* ‘Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model’ by Kikuchi et al. was published in Nature on Wednesday 30th August.
‡ ‘MHC matching improves engraftment of iPSC-derived neurons in non-human primates’ by Morizane et al. was published in Nature Communications on Wednesday 30 August.
Declared interests
Dr Tilo Kunath: No conflicts of interest.
Prof Tom Foltynie: “I have received European Union grant funding as a Co-investigator for the TRANSEURO cell transplantation programme for Parkinson’s disease. No other conflicts of interest.”
Dr David Dexter: No conflicts of interest.