Of the top 10 causes of death in the United States, Alzheimer's disease is the only one that cannot be prevented, cured, or slowed.
However, researchers at Duke University might be one step closer to finding a cure for this devastating disease that affects nearly 5.3 million Americans.
In a recent study, Duke researchers devised a way to prevent immune cells from attacking a vital nutrient in the brain, which causes the memory loss associated with Alzheimer's. So far they've only tested their treatment on mice, but human tests might not be far off.
Carol Colton, a professor of Neurology at Duke University and the senior author of this study, says the key to a cure is understanding how the immune system reacts to Alzheimer's disease. Increasingly, evidence supports the idea that the immune system, which protects our bodies from foreign invaders, plays a part in actually contributing to the disease.
“The [immune cell] response is basically a warrior response where they’re defensive—they fight off bacteria and viruses, and that’s a really good thing,” says Colton. “And then there’s another response to microglia immune cells in the brain, and that is the nurturer, which helps the brain survive, repair, and maintain. It’s easy to see that the warrior would be a component of Alzheimer’s disease, but it’s hard to understand that the nurturer could be a problem in Alzheimer's disease.”
Microglia are known as the first responders to infection, and the research done by Duke shows that they begin to divide and change early in Alzheimer’s disease.
“Our study shows that in fact the nurturer here is a problem,” says Colton. “The immune cell—our microglia—is actually saying ‘I’m unhappy, the brain is unhappy, and I’m going to try to fix it’...It’s just a consequence of overactivity of the system in a confined space.”
Colton and her team found that the microglia immune cells are chewing up an important amino acid, arginine, which is potentially causing Alzheimer's disease. But when it comes to therapies, Colton says that people can’t just eat more arginine or take arginine dietary supplements.
“In reality, you can consume a lot of different types of metabolites, arginine included, but that doesn’t mean they’re going to cross the blood brain barrier,” which determines how much arginine will enter the brain, Colton says. “We have to think about this as a much more complex system than we thought in the past.”
Before the mice began showing Alzheimer’s symptoms, Colton and her team blocked arginase, an enzyme that breaks down arginine, using the drug difluoromethylornithine, also known as DFMO. As a result, the scientists saw fewer microglia and plaques develop in the brains of the mice, and the mice performed better on memory tests.
“DFMO is a very interesting compound because it can be repurposed,” says Colton. “It’s a drug that was used years ago for cancer treatment, it has a very specific activity, and it would be lovely if that drug would actually work in humans for Alzheimer’s disease [AD]. It was never really a particularly good cancer treatment, but it certainly could be repurposed to be a treatment for AD. Are we at that stage that I can say that this is going to be possible, that it can happen, and that it can work? No. We have to be, I would say, cautiously optimistic.”