PD is the most common neurodegenerative movement disorder, characterized by a loss of dopaminergic (DA) neurons in the substantia nigra, degeneration in the brainstem, and loss of other catecholaminergic neurons, which eventually

leads to motor dysfunction and multiple neurological deficits. There is a long history of fetal cell and tissue transplantation to the projection sites of these DA neurons, the caudate-putamen, which has shown some promising results, Caspase inhibitor tempered by the development of disabling dyskinesias in a number of patients (Hagell et al., 2002). Concern has also been raised that engrafted cells may acquire the disease phenotype, as reflected in synuclein aggregates found at autopsy, although the significance of this observation is debated (Isacson and Mendez, 2010). Nevertheless, for some PD patients, engrafted fetal-derived

http://www.selleckchem.com/products/CP-673451.html cells have given long-term relief, providing a rational basis for pursuing stem cell grafts of more uniform, defined cells. Data from such studies indicate that the relevant cell type is an immature A9 type dopaminergic neuron (Grealish et al., 2010 and Mendez et al., 2005). Methods are progressing to differentiate hESCs toward production of these bona fide midbrain DA neurons in sufficiently high numbers for transplantation, and this is likely to be another early indication for an hESC-derived cell product. Another approach for PD being explored by Neurogeneration, Inc. is autologous transplantation of cultured cells derived from cortical and subcortical tissue, which is reported to expand in vitro and produce some catecholaminergic and gabaergic neurons; although the current trial data are limited to a single case report, an autologous approach could be valuable as it avoids immunosuppression. ReNeuron is currently conducting a first-in-human trial for chronic stable stroke, administering fetal-derived allogeneic NSCs conditionally immortalized with c-mycER into the putamen adjacent

to the infarct area, in order to promote surrounding host tissue regenerative responses. Preclinical studies in Vasopressin Receptor rats with middle cerebral artery occlusion demonstrated behavioral recovery in a dose-dependent fashion. NSCs are postulated to release factors that promote vascular growth and restoration of blood supply in damaged areas (Stroemer et al., 2009). It will be important to ascertain how long these cells survive in vivo and, given that the cell product is an immortalized line, to determine the safety profile in humans. Despite the fact that nonneural sources of stem cells do not normally generate bona fide neurons or macroglial progeny, a significant number of CNS clinical trials utilize such cells (see Table 2). In some cases there is clear rationale and evidence for nonneural cells alleviating cell loss or disease in the CNS, e.g.