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Parkinsonian Worms May Hold the Key to Identifying Drugs
Barely visible nematodes like these
share an ancient, conserved
genetic structure with humans.
It's that common genetic heritage
that allows scientists to use the
worms as a model species for
studying Parkinson's disease;
© Marscha Miller
The test is based on the difficulty that these "parkinsonian" C. elegans worms have in switching from swimming to crawling when they are taken out of water.
"They can crawl fine," says Doctor Jon Pierce-Shimomura. "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 to identify this "motor switching" problem. "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.
Pierce-Shimomura has already begun testing potential drugs for Parkinson's. So far he is found one compound that shows promising effects in the worms. The particular compound has already been approved for use in humans for treatment of another condition.
"These worms are so simple to work with, we can do these drug screens at massive scale," says Pierce-Shimomura. "Right now the more hands we have, the more targets we can test."
MEDICA.de; Source: The University of Texas at Austin