Although fetal midbrain cell preparations have been used extensively, very little is known to what extent such GABAergic cells might actually be though counteracting some of the positive effects generated by the DA neurons. In addition,
the 10% DA neurons will consist of both SNc (A9) and ventral tegmental midbrain (VTA, A10) DA neurons. There is selective degeneration Inhibitors,research,lifescience,medical of A9 neurons and a relative sparing of A10 neurons in PD.101-104 These two subpopulations of DA neurons within the SNc serve different functions and project to different brain areas (even within the SNc through dendritic release). The midline-positioned A10 DA neurons105 project primarily to limbic and cortical regions,106 while the neighboring A9 DA neurons (which dysfunction in PD) innervate putamen motor areas.107 Thus, the differences between DA A10 and A9108,109 are significant, and it might be possible to increase the functional effects of DA neuronal transplants by increasing the proportion of A9 neurons compared with A10 Inhibitors,research,lifescience,medical neurons.110-112 Another limiting aspect of cell therapy for PD is the fact that, in most studies, cells have been placed in the ectopic target, area and not in the SNc where the actual degeneration takes Inhibitors,research,lifescience,medical place. Such an ectopic
placement is necessary due to the very limited success of getting DA neurons grafted on the SNc to exhibit long-distance growth and show reestablishment, of the nigrostriatal pathway. The use of stem cells for generating DA neurons for transplantation could allow for genetic or epigenetic manipulations that facilitate target finding and long-distance growth. Another option that is currently under
investigation is grafting to multiple target areas within the basal ganglia Inhibitors,research,lifescience,medical circuit.113 Thus, besides finding the optimal cell source, there are several other Inhibitors,research,lifescience,medical areas such as patient selection, study design, transplantation techniques, target selection, and combination therapies, where considerable improvements can be made14,35,111 before making the final judgment of whether cell transplantation is a useful treatment, for PD. Acknowledgments I acknowledge financial Dacomitinib support from the Swedish Research Council. Selected abbreviations and acronyms DA dopamine EG embryonic germ (cell) ES embryonic stem (cell) FGF fibroblast growth factor GDNF glial cell line-derived neurotrophic factor LIF leukemia inhibitory factor NPC neural progenitor cell PD Parkinson’s disease RA retinoic acid SHH sonic hedgehog SNc substantia nigra compacta
Parkinson’s disease (PD), which afflicts nearly 1 % of the population above the age of 60, is a multisystem neurodegenerative disorder in which progressive loss of midbrain dopamine (DA) neurons, with resulting dopaminergic deafferentation of the basal ganglia, gives rise to characteristic motor disturbances that include slowing of movement, muscular rigidity, and resting tremor. These signs of motor dysfunction, if lateralized, can be clinically Vandetanib order diagnostic of PD.