The replenishment of missing neurons in the brain as a treatment for Parkinson disease reached the stage of human trials over 15 years ago, however the field is still in its infancy. Researchers from Kyoto University have now shown that dopamine-producing neurons (DA neurons) generated from monkey embryonic stem cells and transplanted into areas of the brain where these neurons have degenerated in a monkey model of Parkinson disease, can reverse parkinsonism. Their results appear in the January 3 issue of the Journal of Clinical Investigation.
Studies of animal models of Parkinson disease as well as clinical investigations, have shown that transplantation of fetal DA neurons can relieve the symptoms this disease. However the technical and ethical difficulties in obtaining sufficient and appropriate donor fetal brain tissue have limited the application of this therapy.
These researchers previously demonstrated that mouse embryonic stem cells can differentiate into neurons when cultured under specific conditions. These same culture conditions, technically simple and efficient, were recently applied to primate embryonic stem cells and resulted in the generation of large numbers of DA neurons. In their current JCI study, Jun Takahashi and colleagues generated neurons from monkey embryonic stem cells and exposed these cells to FGF20, a growth factor that is produced exclusively in the area of the brain affected by Parkinson disease and is reported to have a protective effect on DA neurons. The authors observed increased DA neuron development and subsequently transplanted these neurons into monkeys treated with an agent called MPTP, which is considered a primate model for Parkinson disease. These transplanted cells were able to function as DA neurons and diminished Parkinsonian symptoms.
In an accompanying commentary, J. William Langston from the Parkinson's Institute, California, describes this study as a milestone in the development of stem cell technology but cautions that while the observations are encouraging, the reported number of surviving DA neurons was very low, only 1–3% of the cells surviving, well below the estimated number of DA neurons that survive after fetal cell transplants (approximately 10%). While this may be a difference observed between transplantation in monkeys and humans, Langston stresses that it may be necessary for far more DA neurons to survive and for that survival to be long lasting in order to render this approach as a useful therapy in humans.
Langston highlights that "clearly the study reported here will advance research aimed at validating the use of stem cells to treat neurodegenerative disease" and this is most welcome particularly as investigators face yet another presidential moratorium endeavoring to limit the number of human stem cell lines that can be used for future research and treatment.
There are more hurdles here than just making the cells more viable before implanting them. There is the other extreme: the cells should not divide too much and replace more cells than are needed. Also, the cells should replace cells only in the parts of the brain where Parkinson's Disease has caused losses. Though adding extra dopaminergic neurons in small numbers in other parts of the brain might not cause a problem (leaving aside the possibility that a person's personality might change and they might effectively become someone else).
Eventually this work is going to progress to the point that researchers will want to try human trials. In Japan human embryonic stem cell use will probably not elicit much political opposition. So my guess is this avenue of research will eventually progress all the way to useful human therapies. At that point expect a big political fight in the United States over therapeutic cloning to produce human embryonic stem cell lines.
Animal models of diseases are very useful for the development of disease treatments. To use embryonic stem cells in therapy research on other species one must first produce embryonic stem cells. This is difficult to do in some species. In this context it is worth noting that one month ago a team at the University of Pittsburgh reported producing cloned rhesus monkey embryos.
Using newer cloning techniques, including the "gentle squeeze" method described by South Korean researchers who earlier this year reported creating the first cloned human embryonic stem cell line, University of Pittsburgh scientists have taken a significant step toward successful therapeutic cloning of nonhuman primate embryos.
It is the first time researchers have applied methods developed in the Seoul laboratory to nonhuman primate eggs. Resulting cloned embryos progressed to the blastocyst stage, a developmental step in which the embryo resembles a hollow, fluid-filled cavity surrounded by a single layer of cells. Called the inner cell mass, this layer contains embryonic stem cells. Growth of a cloned nonhuman primate egg to the blastocyst stage is farther along the developmental spectrum than ever achieved before, Gerald Schatten, Ph.D., director of the Pittsburgh Development Center at Magee-Womens Research Institute, and his colleagues report.
It remains to be seen whether cells produced using this technique will be a useful source of monkey embryonic stem cells.
So how did the Japanese team get monkey embryonic stem cells for their research? My guess is embryonic stem cells from a conventionally initiated monkey pregnancy was the source. But does anyone reading this know for sure?
|Share |||Randall Parker, 2005 January 04 01:34 PM Brain Disorder Repair|