2002 Route 28 Summit Topic
Stem cell based therapeutic approaches for Parkinson's disease
2002 Summit Topic
Among the disorders of the nervous system that might benefit early from new therapeutic approaches based on the use of stem or other cells, many rank Parkinson's Disease as the likeliest candidate. Not only is Parkinson's Disease a devastating disorder with huge socioeconomic costs, but it is also characterized by a relatively well-understood pathophysiology. Degeneration of a comparatively circumscribed number of dopaminergic neurons in the substantia nigra is the main culprit for the development of the classical symptoms: rigor, tremor and akinesia.
Although the detailed pathological process is complex and hardly understood, it is well-known that replacement of neurotransmitter dopamine to the striatum, the target structure of dopaminergic neurons in the substantia nigra, can relieve symptoms. Systemic application of dopamine and its agonists has limitations, and transplantation of cells releasing dopamine has early been considered a solution to the therapeutic shortcomings in Parkinson's Disease.
The surge in stem cell biology, including neural stem cell biology, in recent years has substantiated these plans. Whereas the transplantation of fetal ventral mesencephalic tissue to the brain of Parkinson patients is hampered by ethical and many technical problems, stem cells with their potentially indefinite renewal and expandability and their potency to develop along several differentiated cellular lineages seem to be the strategy of choice.
Route28 will in 2002 discuss issues that go beyond this straight forward approach. Although Parkinson disease seems to be the ideal candidate for successful cell-based therapy in the adult brain, lessons learned from transplantation of fetal tissue to the brain of Parkinson patients include numerous technical, ethical and practical pitfalls. The intention of the workshop is to develop strategies that include several complementary approaches and try to combine the strengths of for example transplantation with strategies such as deep electrode stimulation. Genetic (or genomic) approaches might facilitate to select donors and recipients, to tailor cell types exactly to ones needs and to develop new technologies of quality control. The point is to play within the limits of feasibility with the opportunities at hand.
As revealed by the list of speakers, there is a strong emphasis on molecular techniques, in particular gene arrays. Gene arrays are extremely powerful tools, but their unwarranted use accumulates useless data and does not lead to exploitable results. With Carolee Barlow and David Lockart we have two experts on our panel, who convey both enthusiasm and a critical attitude towards gene chip analysis. One educational goal of the meeting will be to teach the students a realistic attitude towards this method. With reference to these issues we will discuss genetical models of Parkinson's Disease and the general problem of how well any given animal model can reflect Parkinson's Disease in humans. Several speakers combine a clinical and experimental expertise in the field of Parkinson's Disease. This will give us the opportunity to emphasize the constant need to link experimental results to clinical relevance and applicability.
Many (but not all!) participants of Route28 in 2002 will come from laboratories and departments already involved in research for new experimental strategies for Parkinson disease. For these the workshop will provide the unique opportunity to question their own approach and to benefit from the informal and open discussions.