Autotransplantation for Parkinson’s Disease Goes a Step Further

produce L-DOPA or dopamine. Unfortunately, these grafts (e.g., adrenal medulla) provide only short-term and inconsistent clinical benefits (Gage, 1998) or carry some risk of viral infections. Parkinson's disease (PD) is caused by degeneration of A potential autologous dopamine source that has re-neuromelanin-containing dopaminergic (DA) neurons in ceived little attention until recently is the carotid body. the midbrain substantia nigra, which leads to dopamine The carotid body is located near the bifurcation of the deficiency in the main dopaminergic innervation targets, carotid artery and contains dopamine-rich glomus cells. the caudate nucleus and putamen (collectively called These paraneuronal cells contain chemoreceptors that the striatum). Affected individuals, numbering over a are sensitive to changes in blood oxygen and carbon million in North America, typically exhibit tremor, muscu-dioxide, as well as pH, and they help to regulate respira-lar rigidity, akinesia or bradykinesia (absence or slow-tion rate (Fidone and Gonzalez, 1987). A decrease in ness of voluntary movement), postural instability, and oxygen pressure at the carotid artery induces these cells reduced life expectancy. The best current therapy is the to increase their firing rate and to stimulate medullar dopamine supplement L-DOPA (L-dihydroxyphenylala-neurons that in turn cause a dramatic increase in respira-nine). It is orally active, crosses the blood–brain barrier, tory rate. Thus, these cells thrive and are activated under and can be converted to dopamine by the enzyme DOPA the hypoxic conditions that exist in the graft envi-decarboxylase in the remaining DA neurons and possi-ronment. bly other cell types. Unfortunately, L-DOPA often fails Carotid bodies are not normally essential because to improve tremor, does not always elicit consistent respiratory rate is independently regulated by carbon response, and loses its effectiveness as PD progresses dioxide– and acid-sensitive receptors in the brain stem. and more of the DA neurons that utilize it degenerate. Humans survive unilateral and bilateral resection even L-DOPA also causes significant side effects including though their responses to hypoxia are significantly de-dyskinesias (abnormal involuntary movements) and psy-pressed (Honda, 1992). Autologous transplantation, which chiatric disturbances. Other treatments include dopa-avoids the problem of immune rejection, is thus a real mine agonists (bromocriptine) and monoamine oxidase possibility. A further advantage of the carotid body is B (MAO-B) inhibitors (selegiline), which are often effec-its ability to produce, in addition to dopamine, glial cell tive only early in the course of PD (Lang and Lozano, line–derived neurotrophic factor (GDNF) (Nosrat et al., 1998a, 1998b). 1996), a potent neurotrophic factor …