Going for the Jugular Against Parkinson's

A potential therapy for Parkinson's disease may lie in an unusual location: the carotid body, a small organ in the neck. In the February issue of Neuron, José López-Barneo and his colleagues at the University of Seville in Spain report that in rats, carotid-body cells transplanted from the animals' necks into their brains reverse the symptoms of an experimental form of the neurodegenerative disorder.

The normal job of the carotid body, nestled in the carotid artery, is to signal your brain to step up your breathing if your blood oxygen concentrations drop too low. López-Barneo's main interest had been in how carotid-body cells sense falling blood oxygen levels. But, he recalls, colleagues kept pointing out that these cells might make great candidates for grafting into the brains of Parkinson's patients to correct their deficiencies. That's because the movement problems and other symptoms of the disease are caused by the death of neurons, located in a part of the brain called the substantia nigra, that produce the neurotransmitter dopamine. And because carotid-body cells make lots of dopamine, they might be able to make up for the loss of the normal dopamine-producing neurons.

To find out, the Seville team turned to a common animal model for screening potential Parkinson's therapies. This involves killing substantia nigra neurons on one side of the brains of rats, which then develop a movement imbalance that causes them to turn in circles, as well as exhibiting other symptoms. When the researchers transplanted chunks of carotid bodies into the damaged side of the rats' brains, they found that the transplants not only survived but reversed the animals' symptoms, including the movement imbalance. There were even hints that the cells might be producing growth factors that encourage the remaining substantia nigra cells to sprout new connections.

These results are "quite intriguing, quite promising," says neuroscientist Arnon Rosenthal, who works on therapies for Parkinson's at the biotech firm Genentech Inc. in South San Francisco. Carotid-body cells will have to pass many more tests before researchers can even consider trying them on patients. However, Rosenthal says, they may have an advantage over one competing potential therapy: grafts of fetal neurons. Because carotid cells produce so much dopamine--up to 45 times more than the fetal neurons--and because they thrive in the relatively low oxygen concentrations found in the brain, he explains, they may do a better job at correcting Parkinson's symptoms than the fetal cells do--and they raise fewer ethical questions.

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