Cell transplantation for Parkinson’s Disease. Double grafting into the striatum and substantia nigra as the ideal therapy?

Parkinson’s Disease (PD) is a progressive neurodegenerative disease which belongs to the movement disorders and has a prevalence of about 1% of the total population. In PD the substantia nigra pars compacta (SNc) of the basal ganglia is affected by the atrophy of nigro-striatal dopaminergic neurons, causing a severe loss of dopamine in the striatum, resulting in the inability to regulate normal movements. Many treatments and therapies (e.g. L-Dopa and DBS) exist to relieve PD patients from their symptoms, although most of these cannot repair the core problem. Cell transplantation has provided a new promising strategy for treating neurodegenerative diseases. Foetal mesencephalic tissue and stem cells have shown to be successfully grafted into the striatum and are able to re-innervate the striatum and subsequently release dopamine. Behavioural improvements concerning movement were observed and to some extent patients could be withdrawn from L-dopa. Currently, most of the cells are grafted ectopically into the striatum. However, intrastriatal transplantation cannot provide a long-term remedy for PD and troublesome problems (e.g. dyskinesias) can arise. A possible therapy to repair the origin of the disease might be transplanting stem cells into the physiological area, the SNc. Rodent and human studies have proven that intranigral and double grafting of dopamine neuroblasts is feasible and safe. Results have shown that the grafted cells were able to grow for long distances to the striatum and rewire with the nigro-striatal pathway, resulting in an improvement of the PD symptoms. Moreover, intranigral transplantation showed faster improvements and is able to reconstruct the degenerated nigro-striatal pathway, compared to intrastriatal transplantation. Furthermore, reconstructing the pathway with sufficient dopamine neurons and projections to the striatum, may provide a long-term treatment and possibly a cure to the pathogenesis of this disease