Nice Catch

Undergraduate's "fishing expedition" yields possible new drug to fight brain tumors

By Michael Seele
Chronicle Editor

When Michaela Ranes was assigned to go on a "fishing expedition" as an undergraduate in Prof. Thomas Seyfried's (Biology) laboratory, she didn't expect to catch anything. But she wound up landing a rare prize indeed: a new use for a promising drug to treat brain tumors.

Seyfried said such an accomplishment is quite rare for an undergraduate anywhere, and likely the first such feat for a BC biology undergraduate. As a result of Ranes' work, a biotechnology company interested in the research is funding continuing work in Seyfried's lab to the amount of $189,000 per year. In addition, a pending agreement with a second biotech firm could produce more support for the lab.

Ranes, who graduated in May and is continuing the research as a master's degree candidate, began work on the project through a University summer research fellowship prior to her senior year. Seyfried assigned her to look into alternate uses for a failed AIDS drug, N-butyldeoxynojirimycin. His hunch was that the drug might be useful in inhibiting the growth of brain tumors, something no other drug can do.

Following standard procedure, tumors of various types were implanted in mice and the drug's effectiveness was tested. Ranes said she could see quickly that the mice treated with the drug had much smaller tumors than the mice in the control group.

"It had a very dramatic effect on tumor volume," said Ranes, who is now working on preparing the data for publication. "That was evident within the first couple of months."

Michaela Ranes. (Photo by Lee Pellegrini)
Though Ranes and others in the lab are now trying to determine exactly how the drug works, European researchers are planning to test its effectiveness in human clinical trials. Seyfried hypothesizes that the drug inhibits a growth factor produced by the body's immune cells. In most cases of injury or disease, the growth factor repairs damage, but in cancer cells it has the opposite effect.

"The tumor grows faster," said Seyfried. "The very cells that are supposed to put out the fire are actually throwing gasoline on it."

While the drug did not eliminate the tumors, it slowed them down by about 60 percent of their normal growth rate. Should the drug prove as effective in humans, he said, it could prolong the lives of brain cancer patients whose only current treatment option is surgical removal of the tumor, followed by radiation therapy. The tumors, however, normally regrow quickly and aggressively, and 90 percent of patients die within a year of exhibiting symptoms. Faced with this grim prognosis, Seyfried added, an increasing number of patients, particularly the elderly, are foregoing treatment altogether.

While offering patients more time, a drug that slows tumor growth also could make the cancer vulnerable to other forms of treatment, Seyfried suggested. And, importantly, it does not have the harsh side effects common to chemotherapeutic drugs.

In addition to demonstrating that the drug slows tumor growth, Ranes' research shows that the drug penetrates the difficult barrier between brain cells and the bloodstream that has made treatment of neurological cancers so difficult.

"There are no drugs we know of that can do this in a brain tumor," Seyfried said.

Next year, Ranes will study at Oxford University, where researchers have been working with Seyfreid's lab on the project. Afterward, she plans to attend medical school.

"This whole experience has enhanced that goal," said Ranes. "Clinical research is integral to the practice of medicine, and it is possible to do both."

Seyfried said he could not have sent Ranes on this "fishing expedition" without the University's support. By picking up the cost of animal care and Rane's summer fellowship, he said, the University made this risky experiment possible.

"Boston College policy allows undergraduates to do this," he said. "We would not be able to do this at another university." In this case, he said, the risk was worth taking.

"The project really has mushroomed into something much more that we imagined," he added. "You never know where an undergraduate project might take you."

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