UW breakthrough could combat neurological diseases

By Aaron Nathans, Capital Times

A team of University of Wisconsin-Madison researchers have found a way to revive dying brain cells in lab mice, spurring hopes of combating major human neurological diseases.

“It’s actually amazing,” said Jeff Johnson, an associate professor in the School of Pharmacy and the lead researcher. He said the discovery can be put to work trying to halt the progression of early-stage diseases like Huntington’s, Parkinson’s, Lou Gehrig’s and Alzheimer’s.

Johnson’s team made the findings about two months ago, and fast-tracked the publication process. Marcus Calkins, a molecular and environmental toxicology graduate student in Johnson’s lab, performed key research. It appears in Monday’s edition of the Proceedings of the National Academy of Sciences.

Although the common human neurodegenerative diseases are in many ways different, they have in common the way that brain cells die. Brain cells have natural defense mechanisms that begin to fail as a person ages. In some people, that means long, slow diseases that overwhelm a brain’s defense mechanisms.

Johnson’s team, however, found that when a substance called Nrf-2 is inserted into cells, it revives the defense mechanisms. They determined this by transplanting cells high in Nrf-2 into the brains of mice.

Five weeks later, they exposed the mice to toxins that destroy neurons, similar to the way neurons die in Huntington’s disease. But the Nrf-2 protected the mice from the toxicity, Johnson said.

“We can put the cells in one side of the brain, and put control cells in the other side of the brain. If you give the toxin to both sides of the brain, there’s a physical hole in the side where you put the control cells in,” Johnson said.

“Could we not only protect the cells we transplant, but protect all the cells in that region? Sure enough it worked!” Johnson said, laughing.

Johnson’s method is a novel way to attack the diseases, different from the more controversial stem cell research, said Cindy Lawler, program director at the National Institute of Environmental Health Sciences, which is funding Johnson’s research.

Current therapies for Parkinson’s disease treat the symptoms, but do nothing stop the cells from dying, she said in a telephone interview from North Carolina.

“So there’s lots of interest in developing some new way to protect cells against death, rather than trying to replace the lost dopamine,” Lawler said. “We’re looking at a whole new type of therapy, really harnessing what brain cells normally try to do to protect themselves. Although there are clearly lots of challenges to translating it (to humans), he’s in a very good position to start doing that quickly.”

“He’s really a star. We’re expecting big things from him,” she added of Johnson.

Currently, Johnson’s team is working on learning more about how long mice live with the Huntington’s disease model, once they have received the Nrf-2. The next step would be to develop a pill that would allow humans to “turn up” their own Nrf-2 production to combat the diseases, he said.

Potentially, scientists could use the findings to transplant Nrf-2 directly into the brains of patients who are genetically predisposed to Huntington’s disease, he said. That scenario, he acknowledged, is not likely to occur anytime soon. That is “like Star Trek stuff right now,” he said.