Genetically Modified Cells as a Source for Grafting in Parkinson's Disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease and affects almost 1% of the population above the age of 50. PD was first described by James Parkinson in 1817. His essay on the “Shaking Palsy” reported the major symptoms of the disease, such as bradykinesia, resting tremor, and muscular rigidity (Parkinson, 2002). Most patients exhibit vegetative disturbances, with up to a third showing significant cognitive dysfunction (Lang and Lozano, 1998a,b), and almost 40% of PD patients are affected by depression (Oertel et al., 2001). The most conspicuous neuropathologic finding in PD is the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). In the mammalian ventral midbrain, DA neurons can be found in three different regions, the SNc, the ventral tegmental area (VTA), and the retrorubral field. DA neurons of the VTA project to the ventromedial striatum and cortical area and form the mesolimbic pathway, which is involved in emotional behavior and motivation. DA neurons in the SNc project to the dorsolateral striatum and release DA, an important neurotransmitter which controls movement. Thus, the loss of DA neurons of the SNc leads to a reduction of striatal DA levels (Agid, 1991), that is responsible for some of the cardinal symptoms of Parkinson’s disease. Currently, there is no treatment that can prevent or retard progression of the disease. Since the late 1960s, the main approach to treating PD has been the pharmacological alleviation of the symptoms caused by the striatal