A-beta might reduce damage to central nervous system
A much-maligned molecule that is devastating in the brain may have therapeutic potential outside it. The sticky amyloid-beta protein, which piles up in the brains of people with Alzheimer’s disease, actually reverses paralysis in mice with symptoms of multiple sclerosis.
The unexpected finding, published in the Aug. 1 Science Translational Medicine, could mean that A-beta or molecules like it may one day form the basis of a treatment for multiple sclerosis in people.
In MS, rogue immune cells penetrate the brain and spinal cord and attack myelin, a substance that is necessary to keep neural impulses moving at full speed. Damage and inflammation from this attack can leave a person with paralysis, numbness, vision problems and extreme fatigue.
A-beta is found in the brains of people with MS, but scientists do not know precisely what effect it has there, if any. To investigate that question, study coauthor Lawrence Steinman of Stanford University and colleagues tried injecting A-beta into mice’s abdomens, thinking it would worsen symptoms. “We expected that either nothing would happen or the disease would worsen because this is an infamous, villainous molecule,” he says.
Instead, the mice got better. In several different kinds of mice designed to have symptoms similar to the human disease, A-beta injections into the body reduced paralysis and lowered brain inflammation. “The outcome was unmistakable,” Steinman says.
To do its good work, A-beta didn’t need to enter the brain, the researchers think. After the experiments, there was no evidence of the molecule piling up there. Instead, A-beta exerted its protective effects from the rest of the body, perhaps by calming down immune cells circulating in the blood and preventing them from waging war on the brain.
The data look convincing, but it’s not clear exactly how A-beta works to ease multiple sclerosis symptoms, says biochemist Charles Glabe of the University of California, Irvine. More studies are needed to clarify how A-beta interacts with the immune system, he says.
Other proteins similar to A-beta in shape may bring the same benefit, and without the potential dangers associated with A-beta. Steinman and his colleagues are currently testing other candidates.
Much more work needs to happen before such a treatment could be developed for use in people. “For these approaches, we have to learn what the drawbacks are,” Steinman says. Dampening the immune system could heighten the risk of brain infection, for instance. And there’s always a possibility that the results in mice won’t hold up in humans.
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