UT researchers use worms in Alzheimer's study

— University of Texas researchers Adela Ben-Yakar and Jon Pierce-Shimomura are on a mission. It’s professional, personal and not conducive to patience.

Armed with a five-year, $3 million grant from the National Institutes of Health for “exceptionally innovative” research projects that can shift science in new directions, the two colleagues are devoting a large part of their professional lives to collaborating on new drug therapies for Alzheimer’s disease that might also slow down the aging process. It’s personal because Ben-Yakar’s mother has Alzheimer’s disease and is deteriorating. Pierce-Shimomura’s 10-year-old son has Down syndrome, which causes premature aging and a high risk of developing memory-stealing Alzheimer’s.

“I got into this because of him,” said Pierce-Shimomura, an assistant professor in neurobiology.

Ben-Yakar, an associate professor of mechanical engineering, echoes that sentiment. “I’m losing her every day,” she said of her 78-year-old mother.

Neither has the time to be patient. Perhaps that is why they have turned to roundworms, rather than the traditional lab mice, for their drug studies.

The two are testing chemicals on minuscule worms, called C. elegans, because of the worms’ brief life span — about 15 days — and the quick results that can be gathered when testing drugs on them.

The primitive worms share essential biological characteristics with humans, making them an effective tool for researchers.

“If we give the worm an extra copy of a gene, it contributes to the protein that makes up Alzheimer plaques,” Pierce-Shimomura said. “When worms get that gene, they develop the disease in middle age.”

The worms reach middle age in about five days; mice would take two years, Pierce-Shimomura said.

The researchers can peer at the transparent worms with a fluorescent microscope — an area of Ben-Yakar’s expertise — and see the nerve cells dying.

They also can test to see whether any chemicals delay the degeneration of the neurons, Ben-Yakar said.

She has pioneered a device using microtechnologies to manipulate a large group of worms at once, making the process more efficient and faster than manipulating the worms manually, one at a time.

As a result, she and Pierce-Shimomura can use the nation’s vast drug library to test a million drugs a year, rather than just a thousand.

Without the ability to manipulate the worms and treat with chemical compounds in this manner, “it would take 1,000 years to test 1 million drugs,” Ben-Yakar said.

In addition to testing drugs that might delay or even prevent Alzheimer’s disease, “the goal is to discover drugs we don’t even know about,” Ben-Yakar said.

One drug they are experimenting with has been working well in the worms and also has shown promise in rodent and human trials, the researchers said. They declined to name the drug, saying they first need to publish the results.

Their work has just begun, and so far, they have tested only about a dozen compounds, Pierce-Shimomura said.