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MS-Resistant Mice
December 30, 1999

More than 350,000 people in the United States suffer from multiple sclerosis (MS), and doctors are still searching for a cure. But scientists are finding that genetically altered mice may hold a key that could unlock the mysteries of this mysterious and debilitating disease.

Researchers at the University of Alabama at Birmingham (UAB) have discovered a way to insert a gene in mice that protects them from an animal form of MS. These genetically-modified mice produce a brain protein called "sCrry" (pronounced "scurry") that changes the way their immune system works. "We found that we could block the disease completely or significantly delay its onset," says Scott Barnum, a senior author of the study reported in the Journal of Immunology.

How Does It Work?

image: Natl. MS Society

The cause of MS is not well understood, but most scientists agree that MS is a type of autoimmune disease. Individuals with MS have T-cells that attack a fatty substance called myelin. Myelin is found wrapped around nerve fibers, thereby insulating the nerve signals. Consequently, signals from neurons with damaged myelin become "short-circuited" on their way to and from the brain. This disruption causes symptoms such as blurred vision, slurred speech, paralysis, and numbness. "Normally, you should have T-cells and B-cells that are reactive only against foreign pathogens," explains Barnum, "not your own tissue."

The MS autoimmune response can be divided into two components. First, something causes part of the immune system to become confused while identifying what should be attacked. Second, another part of the immune system responds to the attack signal by gathering at the identified site, causing inflammation and swelling. This inflammation response can dangerously bruise the brain, leading to further damage.

But the sCrry protein acts to "turn off" the inflammation response. "By blocking the inflammatory component," says Barnum, "it may be possible to significantly reduce the amount of damage that occurs when these MS lesions begin to develop."

What Does This Mean for MS Sufferers?

Everyday tasks are difficult for those with MS.
image: Natl. MS Society

It’s not a cure, but creation of drugs that work like the sCrry protein may offer doctors a strategy to minimize the damage caused by the disease. "It suggests there’s another direction to take in terms of research to try to understand how the disease develops and how we might block it," says Barnum.

As with promising research in any animal model, scientists must prove that the same disease mechanisms and inflammation-suppression strategies work in humans. There may be significant differences. For one thing, mice do not normally develop MS; scientists must induce the disease in them by injecting a particular protein that triggers an MS-like response.

Scott Barnum

An additional concern is that turning off the inflammation response could potentially leave a person immuno-compromised and susceptible to infection. "But the central nervous system (CNS) is kind of an enclosed separate compartment," argues Barnum. "So if you deliver a drug just to the CNS to block response activation, theoretically, it should block response activation only in the CNS and not throughout the entire body."

The researchers at UAB are making their genetically modified mice available to other scientists to determine whether the sCrry protein offers protection against other inflammatory diseases. This may offer additional hope down the road to patients of Alzheimer’s, Mad Cow Disease, and Bacterial Meningitis.

Elsewhere on the web:

The National MS Society

The International MS Support Foundation

The Multiple Sclerosis Association of America



by STN2


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