Auto Transplants for Parkinson's Disease?

Abstract

94080 in the globus pallidus (pallidotomy) have been tried. Pallidotomy was practiced prior to the development of The Disease L-DOPA, discarded, and recently regained acceptance Parkinson's disease is the third most common neurode- (Lang et al., 1997). The rationale behind pallidotomy is generative disorder, with a prevalence of approximately easy to understand. Since in the absence of dopaminer-1% of the population over 65. Affected individuals suffer gic inputs the globus pallidus is hyperactive, selective from debilitating deficiencies in motor functions that lesions will weaken its activity and reduce it to normal manifest in (1) rhythmic tremors at rest, (2) inability to levels. Similar rationale also led to the usage of highinitiate (akinesia) or complete (bradykinesia) routine frequency (inhibitory) electrical stimulation in the submovements, (3) muscle rigidity that leads to jerked mothalamic nucleus. The subthalamic nucleus normally tions, (4) postural instability, and (5) lack of facial expresstimulates the globus pallidus, and its inhibition helps sion. The disease is predominantly nonfamilial and does reduce globus pallidus activity (Figure 1). not show gender or racial bias. It is invariably progres-Although pallidotomy and electrical stimulation show sive and 5-10 years after onset the worst patients are promise in reducing akinesia and bradykinesia-espeleft bedridden and die of infections or secondary complicially akinesia that is induced by L-DOPA in advanced cations.Parkinson's patients-they are not consistently effec-The clinical symptoms are caused by a selective loss tive in reducing tremors. In addition, many symptoms of pigmented dopamine-producing neurons from the recur after only a few years. Thus, a third therapeutic substantia nigra in the midbrain and a consequent deapproach was called for-transplantation (Yurek and crease in dopamine at the innervation targets of these Sladek, 1990). The rationale behind transplantation for neurons, which include the striatum, cortex, and nucleus Parkinson's disease is again straightforward: the idea accumbens.is to replace lost dopaminergic neurons with a graft of The cause of cell death in Parkinson's disease is unnew embryonic neurons. Transplantation of fetal dopaknown. Viral infections, environmental toxins, and oxidaminergic neurons into rodent models of Parkinson's distive stress induced by dopamine metabolites, are all ease was pioneered in the early 1980s (Bjo ¨rklund and suspected. In contrast, the consequence of dopaminer- Stenevi, 1979;Perlow et al., 1979). In these initial experigic neuron loss for the neural circuits that control movements, approximately 150,000 ventral midbrain neural ment is well understood. The dopaminergic neurons are

Selective Glial Cell Line-Derived Neurotrophic Factor Production in Adult Dopaminergic Carotid Body CellsIn Situand after Intrastriatal Transplantation

“…However, unequivocal evidence for GDNF expression in CB of adult rodents was obtained from heterozygous knock-out GDNF/lacZ mice, in which the cells expressing GDNF contain ␤-galactosidase deposits that can be labeled with the characteristic blue X-gal staining . Using this experimental tool, we compared the level of GDNF expression in the CB and that in the AM, SCG, or retina, which are catecholaminergic donor tissues used in transplantation studies to treat PD in animals and humans (Bohn et al, 1987;Itakura et al, 1988;Yurek and Sladek, 1990;Rosenthal, 1998). The histological illustrations in Figure 1 clearly show the high level of GDNF expression in the CB (blue-green color deposits in A) and its complete absence in the AM (C, D), SCG (E, F ), and retina (G, H ).…”

Challenges in tissue engineering

“…Fetal human mesencephalic cells (which include dopaminergic neural stem cells) were the first cells to be transplanted in an attempt to cure Parkinson's disease (Rosenthal 1998). When injected into the striatum of Parkinson's patients, they differentiate into dopaminergic neurons (DANs) and make synaptic connections with host neurons, restoring the activity of the striatopallidothalamic output pathway toward normal.…”

Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes

“…Functional replacement of specific neuronal populations through transplantation of neural tissue represents an attractive therapeutic strategy for treating neurodegenerative disorders such as Parkinson's disease 1 . Recent advances in neural stem cell biology have shown that multipotent neural progenitors can be isolated, expanded, and used as source material for brain transplants [1][2][3][4][5][6][7][8] .…”