UW-Madison researchers have found a protein that may stop the progression of neurological diseases such as Huntington’s, Parkinson’s, Lou Gehrig’s and Alzheimer’s. “Scientifically, I still have trouble believing it,” said Jeff Johnson, UW-Madison associate pharmacy professor and the lead researcher. “If we can learn to modulate (the protein) in the central nervous system, we really could have an impact on a number of diseases.”
In research published Tuesday in the Proceedings of the National Academy of Sciences, Johnson and others report that the protein Nrf-2 turns on cellular self-defenses, preventing cell death.
The researchers took cells with high levels of Nrf-2 and implanted them into the brains of mice. They then exposed the mice to toxins that kill nerve cells, similar to what happens in patients with those neurological diseases. “It completely protects them,” Johnson said. “It’s amazing.”
Next, researchers must begin testing this on primates and people. “It’s still pretty early in the game, but it would be really great if something came out of it therapeutically,” said Marcus Calkins, 28, a doctoral student who worked on the project under Johnson’s supervision. Calkins and others in Johnson’s lab are now searching for a molecule that could activate Nrf-2 in the brain. They’re already testing several possibilities, Johnson said, and he hopes to have a pill ready for human testing in two to four years.
It can’t come soon enough for John and Cheryl Sandner of McFarland. John Sandner, 57, was diagnosed with Lou Gehrig’s disease, or amyotrophic lateral sclerosis, about four years ago and is now in a wheelchair. He still breathes well on his own, can swallow and talk. “I’ve been really lucky so far,” Sandner said. “I’ve already outlived several of my colleagues, fellow patients with ALS. I’m hoping very much that one of these things like what Dr. Johnson is working on will come through for me.”
Researchers are also looking at implanting cells containing Nrf-2 into the brains of patients with these degenerative neurological diseases. It’s especially promising for Huntington’s disease, which is caused by an abnormal gene, Johnson said. People with that gene will get the fatal disease, but Johnson said he hopes transplanting these cells could stop it before it starts. That option will take more time and research than developing a pill, he said.
Nrf-2 works with about 100 genes to turn on elaborate systems cells use to protect themselves from toxins in the environment and those that naturally occur in the body, Johnson said. These defenses become less efficient with age. The protein appears to work to stop Huntington’s, Parkinson’s, Lou Gehrig’s and Alzheimer’s because although all four of these diseases kill different cells, the way those cells die is similar, Johnson said.
Researchers elsewhere are working on better diagnostic tools to help people diagnose these degenerative diseases earlier, Johnson said. “We can intervene much earlier in the pathologic process,” he said, “and prevent the subsequent damage from occurring.
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Created: Mar. 6, 2005
Last updated: Nov. 15, 2010