University of Maryland grad student restores movement to mice crippled with multiple sclerosis

Crippled by multiple sclerosis, the lab mice's hind legs and tails were limp with paralysis, but Lisa Tostanoski had an idea about how she could treat them.

With a tiny needle, the doctoral student at the University of Maryland, College Park injected the mice with a dose of time-released medicine. Two weeks later the mice were scampering around their cages.

"They were able to stand up on their hind legs," Tostanoski said. "We reversed the paralysis."

The treatment, a complex combination of immunology and engineering, earned Tostanoski, 26, a prestigious Lemelson-MIT Student Prize, awarded to her and eight other students and teams earlier this month. The prize for the most promising young inventors in America awards her $15,000 for her medical invention to reverse symptoms of debilitating autoimmune diseases such as multiple sclerosis. Her novel approach has shown promise for developing treatments in an area that has long eluded researchers.

"If her invention that she's working on proves successful, it's a game changer," said Stephanie Couch, executive director of the Lemelson-MIT Program. "She didn't shy away from something that seems big and daunting."

Autoimmune diseases occur when a person's immune system mistakes healthy cells in the body for a foreign threat and attacks the tissue. With multiple sclerosis — a disease afflicting more than 2.3 million people worldwide — the immune system's defense cells attack the fatty myelin sheaths that cover nerves. Researchers don't know why these confused "T-cells" attack. But persistent barrages can damage nerves, causing muscles to weaken and stiffen, and lead to paralysis.

Doctors routinely treat multiple sclerosis patients with medicine to suppress the entire immune system and stave off attacks. But this strategy has widespread and often dangerous side effects in the body, and the benefits diminish over time.

Tostanoski, a McDonogh School alumnae from Catonsville, working in University of Maryland bioengineering lab, has embraced a different approach: transform the T-cells.

She began experimenting five years ago to develop a method to target the bad T-cells. Such a treatment would transform care for millions of people with multiple sclerosis.

"It's the Holy Grail of MS. Finding the exact T-cells that are causing the disease and getting rid of them could be close to a cure," said Bruce Bebo, executive vice president for research at the National Multiple Sclerosis Society in Waltham, Mass. "By selectively targeting the T-cells, you might be able to stop MS in its tracks."

The National Multiple Sclerosis Society has spent nearly $650,000 to fund Tostanoski's work at the Jewell Research Lab in College Park. Elsewhere, researchers are trying to develop similar pinpoint treatments that leave immune systems unscathed. The society has committed $80 million over the next four years to fund more than 300 research projects around the country.

Rather than suppressing the bad T-cells, Tostanoski's method aims to change the cells from foe to friend within the lymph nodes. These glands swell to produce defense cells when a person becomes sick.

"Think of the lymph nodes like a classroom," she said. "Cells that recognize myelin learn to mature and become inflammatory, then travel out of the lymph node to the brain where they attack."

She injected tiny fragments of myelin into this lymph node classroom. But her breakthrough came when she encapsulated the fragments with a coating that gradually wears down to prolong the release of myelin.

"You're basically keeping the stuff around longer," said Christopher Jewell, an associate professor of bioengineering who runs the College Park lab. "If you just inject something in there, it could flow out and be gone."

T-cells that develop in the presence of myelin don't attack it, though researchers don't know why. These cells will leave the lymph nodes and actually defend myelin. They also will calm the attacking cells.

The concept was born from theories that injections with low doses of bee pollen will diminish someone's allergy to bees. In two weeks of myelin treatments, the lab mice gradually recovered.

"What's really unique about what Lisa's working on is depositing in the lymph node and controlling the release," said Jewell, her academic adviser.

By focusing on multiple sclerosis, Tostanoski took on a large and vexing medical riddle, which attracted the Lemelson prize judges. Among the recent winners were students who developed a folding drone, an advanced prosthetic foot, a protein to fight superbug bacteria, and a portable device to convert text to Braille.

Multiple sclerosis is two to three times more common in women than men, according to the society. Most people are diagnosed between the ages of 20 and 50. The average American has about a one in 750 chance of contracting multiple sclerosis, according to the MS society.

Further research remains before Tostanoski's treatment is tested on people with MS. Researchers in the College Park lab plan to next test her methods on human lymph nodes removed during biopsies.

Tostanoski expects to receive her Ph.D. in bioengineering in the coming months, and she intends to find a research job with a university and one day become a professor. Researchers at the University of Maryland will carry on her work.

For now, she's relishing her award from the Lemelson judges. She learned of their decision by voice mail.

She was busy in the lab when they called.

tprudente@baltsun.com

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