Transplantation studies in animal models of Parkinson�'s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder, resulting from the loss of dopaminergic (DA-ergic) neurons from the substantia nigra pars compacta (SNpc) region of the brain. These cells form an integral part of the basal ganglia, an area responsible for motor coordination in mammals. In humans and subhuman primates, loss of these cells results in akinesia, rigidity, postural instability and tremor, and these symptoms progress as the loss of neurons from this region accelerates. Cell replacement therapy is considered as an obvious option for the recovery of lost motor functions resulting from the loss of neurons. This is relevant for PD owing to failures of available pharmacological approaches. Moreover, it was thought to be theoretically feasible because of the loss of only a particular segment of the CNS DA-ergic systems, the A9 DA-ergic neurons, the terminals of which are in each of the striatum. Additionally, the anatomical location of the terminal region is an accessible site for any surgical interventions. A simple technique of placing dopamine secreting cells at the site of the A9 SNpc neuronal terminals would provide the neurotransmitter required for stimulating postsynaptic neurons in the area. The next problem could be engineering the transplanted neurons to release dopamine to specific stimuli. However, in practice, even transplanting dopamine releasing neurons in the striatum met with difficulties. To add to the woes, the varied outcomes of transplantation studies made it difficult to decipher the exact problem(s). Ultimately, what remains as of now are a bunch of speculations in regard to the failures or inconclusive outcomes of this therapeutic option. The major problems associated with cell replacement therapy in PD seem to be (i) the availability of implant material, (ii) its source, (iii) nature of the material, (iv) survivability of the cells in the grafts, and finally (v) fate of the transplants in long term grafts. Last, but not the least, the graft associated abnormalities in the host is a major unresolved issue