Stem Cells and Parkinson’s Disease: Promise

The majority of clinical research concerning Parkinson’s Disease has so far concentrated on improving drug development and activity, but stem cell research is focused mainly on regenerating those nerve cells which are responsible for dopamine production and halting the progressive destruction of such cells. Stem cell therapy for Parkinson’s Disease holds great potential as the disease is connected, for the most part, to a very specific cell type which could, theoretically, be regenerated in order to restore function and reduce symptoms.

Clinical Trials for Stem Cell Parkinson’s Treatments

As yet, no stem cell treatments are available for Parkinson’s Disease although there is one clinical trial currently registered which will investigate adult mesenchymal stem cell transplants for patients with the disease (NCT00976430). Two clinical trials looking at the potential for fetal nigral transplantation did not achieve their aims and were complicated by the development of dyskinesia in patients that remained after withdrawal of levodopa (Snyder, et al, 2005). Further investigation now points to this dyskinesia as a possible sign of partial dopaminergic reinnervation of the striatum however, and the transplantation of more dopamine neurons might actually improve symptoms to the point of clinical significance. These clinical trials in humans have demonstrated the ‘proof-of-principle’ for cell replacement in Parkinson’s Disease, but the variability in individual patient response to the treatment makes the development of a generic stem cell therapy extremely complex.

Stem cell research for Parkinson's has gained popular media attention

Possible Long-Term Benefits of Stem Cell Treatment for Parkinson’s Disease

The ability to use adult stem cells as a source for dopaminergic neurons avoids the ethical considerations of fetal mesencephalic transplants or fetal and embryonic stem cells, meaning that research is slightly less constrained than in previous years. The research in animal models however has so far shown a limited response to the use of neural stem cells with poor cell survival rates. Enhancement of the yield of dopamine neurons from stem cells may help, as will efforts to reduce cell apoptosis. Research using embryonic dopamine neurons transplanted into the diseased brains of Parkinson’s patients found that only a subgroup of the treated patients experienced clinical benefit from the treatment and that 56% of those receiving stem cell therapy experience non-medicated dyksinesia (Freed, et al, 2001). Follow-up analysis of these patients has also uncovered signs of the disease, alongside healthy dopaminergic cells, between nine and thirteen years after treatment which creates concerns over the potential long-term benefits of such stem cell therapy (Li, et al, 2008).

How To Improve Stem Cell Therapy’s Efficacy

It may be that stem cell therapies remain ineffective for Parkinson’s Disease while they concentrate on the dopaminergic neurons alone, as some symptoms are due to degeneration of non-dopaminergic neurons. Understanding the disease’s development more thoroughly is also likely to aid the creation of a direct stem cell treatment. Stem cell research may aid those with Parkinson’s Disease not through direct implantation of stem cells into the brain but by allowing scientists to create models of the disease’s progression in the laboratory on which to investigate new medications and treatments. Medications which encourage neural stem cells to give rise to specific dopamine-producing neural cells, and direct infusion of intraparenchymal neural stem cells may be combined or administered individually in the future treatment of Parkinson’s Disease but such therapies remain theoretical, for the moment at least.

Changing Stem Cell Transplant Placement

The placement of stem cells in the brain is also under considerable discussion as some believe that the dyskinesia experienced by patients in the two clinical trials carried out in humans was a result of non-physiologic dopaminergic activity which could be avoided if the stem cells were alternatively implanted. However, direct implantation of the neural stem cells into the substantia nigra would most likely require additional therapy to bridge the gap between growing axons resulting from the stem cell transplant and the striatum of the adult brain in order to fully address Parkinson’s Disease pathology.

References

Snyder, B.J, Olanow, W.C., (2005), Stem cell treatment for Parkinson’s disease: an update for 2005, Current Opinion in Neurology, Volume 18 – Issue 4 – p 376-385

Li, J.Y., Englund, J.L., et al, Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation, Nature medicine 14 (5) (2008), pp. 501–503.