By Jessica Tobacman, Special to the Tribune
August 15, 2012
Northwestern University and University of Kentucky scientists have created a new drug that could successfully prevent harmful inflammation in brains of people suffering fromAlzheimer's disease.
The scientists, who published their findings in the July 25 issue of the Journal of Neuroscience, said the experimental drug, which is aimed at the central nervous system, also could potentially be used to treat patients with brain injury or trauma, multiple sclerosis andParkinson's disease.
The drug, known as MW-151, is "a very selective blocker of the overproduction of inflammatory molecules," said Linda Van Eldik, director of the University of Kentucky Sanders-Brown Center on Aging and a senior author on the paper. "It brings inflammatory molecules back to normal levels. With inflammation, there's a balance between good and bad inflammation. With inflammation, you want the inflammatory reparative mechanisms to stay and not be blocked. The drug blocks the overproduction of inflammatory responses."
Excessive inflammation harms the brain, she said. "With many of these diseases, too much inflammation tips the scale toward detrimental outcomes. It can create problems with memory and learning. These drugs dampen down the pro-inflammatory (response), and decrease synaptic problems and nerve damage," Van Eldik said.
Dr. Martin Watterson, a professor of molecular biology and biochemistry at Northwestern University's Feinberg School of Medicine, said the new drug works well when used with other medications.
"I feel good that, if money can be raised (to commercially produce the drug,) it will be very useful in combination with other drugs," Watterson said. "The drug is designed to be safe with other drugs, not to conflict with them. I'm not prone to easy enthusiasm … but as we go farther along, my enthusiasm increases."
The study used mice to determine whether the drug is more effective against Alzheimer's disease at a later or earlier point in the illness. The first group of mice were about 6 months old when they first received either the new anti-inflammation drug or a saline solution and continued to receive it three times each week until they were 11 months old. The second group of mice were 11 months old at the outset and received the new anti-inflammation drug or a saline solution every day for a week. The saline solution served as the placebo in the test.
Within each group, the healthy mice received saline; one group of diseased mice who showed some features of Alzheimer's disease were also given saline; and a third group of mice who showed signs of Alzheimer's received the drug.
"We needed the mouse model to show the problem (of inflammation). The mouse model also showed changes in memory and synaptic problems," Van Eldik said. "The (new anti-inflammation) drug worked under both conditions, but there was a stronger effect if they started early. The mice with the drug looked as if it didn't have Alzheimer's disease. It was normalized. It looked just like the wild type (healthy) mice."
A mouse at 6 months of age is at a point comparable to when a human shows the first signs of Alzheimer's disease, or mild cognitive impairment.
"This was a major endeavor, to show how the pathology timeline in mice related to humans," Watterson said.
The study found that "targeting inflammation can be beneficial in terms of decreasing the progression of the disease, and that the therapeutic window is important to get the best response of the drug. There are more benefits when it's used early," Van Eldik said.
Dr. Ottavio Arancio, an assistant professor of pathology at Columbia University Medical Center, said he's optimistic about the potential of the experimental drug.
"I think the results are very promising. These drugs could help with the disease. They could improve some of the pathology in people with Alzheimer's disease," Arancio said.
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