Parkinsonian worms may hold the key to identifying drugs for Parkinson's disease

November 10, 2011, University of Texas at Austin
Using a method called optogenetics, Jon Pierce-Shimomura can turn targeted genes on and off using light. Credit: Marsha Miller

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 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 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 . "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.

In this video, Jon Pierce-Shimomura, assistant professor of neurobiology, describes the test that is based on the difficulty these "parkinsonian" C. elegans worms have in switching from swimming to crawling when they’re taken out of water. Credit: Mason Jones

"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 in humans.

The dopamine-deficient worms are put through the same paces that lead to the , 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's 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.

Working with the university's Office of Technology Commercialization, he's filed a patent application for the worm model for testing of neurodegenerative diseases such as Alzheimer's and Parkinson's.

About half a million Americans suffer from Parkinson's disease, a degenerative disorder of the central nervous system. Early symptoms of the disease include shaking, rigidity, and slowness of movement. As it progresses, the physical symptoms can advance to the point of incapacity, and cognitive impairments, including early dementia, can arise as well.

A huge barrier to preventing or treating diseases such as Parkinson's is the amount of time it takes to identify drugs that work effectively. Typically, drugs are tested on mice—a process that is expensive and requires one to two years for mice to age while testing just a few dozen drugs at a time.

With the help of a few undergraduates Pierce-Shimomura believes that he can test about 1,000 drugs a year. The number could rise to one million a year if the process can be automated.

He recently received a competitive $3 million Transformative Research Projects Award from the National Institutes of Health with mechanical engineering professor Adela Ben-Yakar, to develop just such an automation process for parkinsonian worms as well as worms mutated to have other neurodegenerative diseases, including a C. elegans version of Alzheimer's.

"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."

Explore further: Reversing aging

Related Stories

Reversing aging

October 17, 2011
Technology developed by researchers at The University of Texas at Austin could significantly reduce the time and cost to finding a cure for Alzheimer's disease and help answer one of the greatest biological questions: why ...

Tiny worms head into the breach as team searches for Parkinson's treatment

June 24, 2011
McMaster researchers from three disciplines are deploying thousands of tiny worms and a homegrown invention to test drugs in a collaborative bid to defeat Parkinson's Disease.

People with Parkinson's more likely to have leg restlessness than restless leg syndrome

November 9, 2011
People with Parkinson's disease may be more likely to have a movement disorder called leg motor restlessness, but not true restless legs syndrome as previous studies have suggested, according to a study published in the Nov. ...

Recommended for you

Investigators eye new target for treating movement disorders

January 19, 2018
Blocking a nerve-cell receptor in part of the brain that coordinates movement could improve the treatment of Parkinson's disease, dyskinesia and other movement disorders, researchers at Vanderbilt University have reported.

Parkinson's disease 'jerking' side effect detected by algorithm

January 8, 2018
A mathematical algorithm that can reliably detect dyskinesia, the side effect from Parkinson's treatment that causes involuntary jerking movements and muscle spasms, could hold the key to improving treatment and for patients ...

New brainstem changes identified in Parkinson's disease

January 4, 2018
A pioneering study has found that patients with Parkinson's disease have more errors in the mitochondrial DNA within the brainstem, leading to increased cell death in that area.

Caffeine level in blood may help diagnose people with Parkinson's disease

January 3, 2018
Testing the level of caffeine in the blood may provide a simple way to aid the diagnosis of Parkinson's disease, according to a study published in the January 3, 2018, online issue of Neurology, the medical journal of the ...

Researchers shed light on why exercise slows progression of Parkinson's disease

December 22, 2017
While vigorous exercise on a treadmill has been shown to slow the progression of Parkinson's disease in patients, the molecular reasons behind it have remained a mystery.

Robotic device improves balance and gait in Parkinson's disease patients

December 19, 2017
Some 50,000 people in the U.S. are diagnosed with Parkinson's disease (PD) every year. The American Institute of Neurology estimates there are one million people affected with this neurodegenerative disorder, with 60 years ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.