Parkinsonian Worms May Hold the Key to Identifying Drugs for Parkinson's Disease

ScienceDaily (Nov. 10, 2011) — Researchers at The University of Texas at Austin have devised a simple test, using dopamine-deficient worms, for identifying drugs that may help people with Parkinson's disease.

The worms are able to evaluate as many as 1,000 potential drugs a year. The researchers have received federal funding that could increase that to one million drug tests a year.

The test is based on the difficulty that these "parkinsonian" C. elegans worms have in switching from swimming to crawling when they're taken out of water.

"They can crawl fine," says Jon Pierce-Shimomura, assistant professor of neurobiology. "They go into a puddle and can swim fine. But as soon as the puddle goes away they crash. In some cases an individual will remain rigid for about a half hour."

Pierce-Shimomura led a team of researchers, including Andres Vidal-Gadea, Stephen Topper and Layla Young, to identify this "motor switching" problem. Their findings were published last month in the Proceedings of the National Academy of Science.

"We take these motor transitions for granted," says Pierce-Shimomura, "like getting up out of a chair or walking through a doorway from one surface to another. But people with Parkinson's have a terrible time with this. They freeze at the threshold. It looks like we have a very simple worm model for this now."

To identify potential therapeutics, Pierce-Shimomura begins with worms that have been mutated to be deficient in producing dopamine. It's the loss of dopamine-producing cells in the brain that causes Parkinson's disease in humans.

The dopamine-deficient worms are put through the same paces that lead to the immobility, but in the presence of a drug.

If they become immobile as they normally would when water is removed, the researchers move on to the next drug. But if somehow a drug helps the worms' brains overcome the dopamine deficiency and they transition to crawling, the lab has a potential therapeutic.

Pierce-Shimomura says that although humans have a vastly more complex nervous system than the worms, the two species share an "ancient and conserved" genetic structure to their dopaminergic systems. What works to overcome a dopamine deficiency in the worms may do something similar in humans, and it can be tested in worms with extraordinary speed.

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