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.
Recently much attention has been focused on the use of stem cells as a potential treatment for Parkinson’s disease (PD). Now, researchers at Memorial Sloan-Kettering Cancer Center in New York City report that they have successfully placed embryonic stem cells into several PD animal models. The findings are published in the November 6 issue of Nature. This month, I will review this exciting paper and outline the “next steps” for stem cell therapy.
In the study, Sonya Kriks, Ph.D., and the research team used embryonic stem cells to generate dopamine neuron cells. Then, they transplanted the new cells into 6-hydroxy-dopamine-lesioned mice and rats (laboratory models with induced Parkinsonism). The new cells reportedly survived, and in two important tests of behavior, the animals’ Parkinsonian symptoms improved. After researchers implanted the new cells into monkeys (which are considered evolutionarily closer to humans) they also found that the cells survived, and test results showed positive behavioral benefits as well. Finally, no tumors were found in the laboratory models, which is important because tumor formation has been an ongoing concern for stem cell biologists interested in translating discoveries from the “bench-to-bedside.”
As patients and families continue to ask the key question, “Why don’t we start transplanting stem cells for this generation of Parkinson’s disease sufferers?” we must keep in mind findings from previous research. In the past, simple cell transplantation experiments proved that, like Dr. Kriks and her team, “we can” place cells in the brain (this was done in human brain), and that with special techniques we can ensure cell survival. Unfortunately, we also have discovered that these transplanted cells can only reconstitute a small percentage of the critically affected brain regions in PD.
Too, we know that with simple cell transplantation, the symptoms addressed are usually motor---tremor, stiffness and slowness. Behavioral issues such as walking, talking and thinking have not been adequately addressed. The reason for this is thought to be related to the complexity of the brain and “neural” circuitry. Also, recent cell transplants in humans have resulted in a difficult-to-treat side effect called “runaway dyskinesia.” And, we know from brains that have been “turned in” (post-mortem brain bank specimens), that transplanted cells have become “sick” with PD proteins that promote disease progression.
That said, this research by Dr. Kriks’ team and other scientists is proving critical in helping to move stem cell research forward and to bring new therapies to people with PD. However, many challenges still need to be overcome before these therapies are ready for prime-time. The new generation of stem cell scientists will have to better address the following: 1. all symptoms of PD (motor and non-motor/behavioral); 2. levodopa resistant symptoms (such as walking, talking and thinking); and 3. how to protect newly transplanted cells against “sickness.” Additionally, any new therapy will need to be proven safe, ensuring runaway behavioral manifestations and other adverse events do not occur. Future models also will need to prevent tumor formation.
We remain encouraged that stem cell therapy can play a role in the treatment of PD in the future, and we look forward to a new generation of scientists who will pursue these current challenges. We congratulate Dr. Kriks and the other study authors for having taken another important step forward. We would encourage stem cell researchers to continue to “think outside the box” and to combine their cell based techniques with novel delivery systems, which we hope will lead to developments of new therapies that will improve and rescue much larger areas of brain in people with PD.
Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR, Xie Z, Carrillo-Reid L, Auyeung G, Antonacci C, Buch A, Yang L, Beal MF, Surmeier DJ, Kordower JH, Tabar V, Studer L. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature. 2011 Nov 6. doi:
10.1038/nature10648. [Epub ahead of print] PubMed PMID: 22056989.