© 1999 Medical PressCorps News Service
Altering protein levels in the immune system may help treat the symptoms of multiple sclerosis, an autoimmune disease that affects nearly 400,000 Americans.
Scientists from the University of Alabama at Birmingham, working with a part of the immune system called the complement system, have successfully treated tissue damage and inflammation in mice with a form of multiple sclerosis.
These study results offer a new avenue of research and a potential treatment for the disease.
"In autoimmune diseases such as multiple sclerosis, the body attacks itself in a confused immune response," said Scott Barnum, assistant professor of microbiology at UAB. He is the lead author of the study, which appeared in the December edition of the Journal of Immunology (http://www.jimmunol.org).
Proteins that inhibit this confused immune response by the complement system may block the progression of multiple sclerosis, he said.
The complement system has more than 18 proteins. Some are activators; others are regulators. Activators fight foreign elements that enter the system, such as bacteria or viruses. Regulators help to stop the activators when the immune response is no longer needed.
In multiple sclerosis, the regulator proteins appear to improperly control the activators, causing the immune system to attack myelin -- insulation found on nerve cells. Damage to myelin results in the symptoms of impaired vision, muscle weakness and incoordination that are characteristic of multiple sclerosis.
In the study, the researchers manipulated a regulator protein, called soluble complement receptor-related protein y, or sCrry, in certain strains of transgenic mice. These animals had a gene added that causes sCrry to be consistently active in the brain. The investigators then injected the mice with peptides that are known to cause symptoms similar to those of multiple sclerosis. However, because the mice had heightened amounts of the regulator protein in their brains, they were able to suppress the activator proteins and were spared of developing any multiple sclerosis symptoms.
"These mice developed no signs of disease whatsoever," said Barnum. They showed no motor difficulties and did not display any damage to the myelin that surrounds the nerve cells, a cellular marker of multiple sclerosis.
Barnum explained that a protein in humans called soluble complement receptor type 1, or sCR1, is similar to the sCrry protein in mice. Currently, other research labs are using sCR1 to help block complement activation in the treatment of diseases that occur outside the central nervous system, he added. As his research progresses, Barnum said, he suspects pharmaceutical companies may turn their attention to studying and treating multiple sclerosis and related diseases with sCR1.
"I think there's hope," Barnum continued. "But I certainly wouldn't project when [a human treatment] might be in use. These are early studies, and I think it will be a few years before we have a better handle on what's going on in a number of diseases and how widely this might be applied. But it's an exciting prospect."
He added that blocking the response of the complement system may help treat a number of conditions, such as stroke, Alzheimer's disease and bacterial meningitis.
"It's an important fundamental research finding related to animal models of MS," said Dr. Stephen Reingold, vice president for research programs for the National Multiple Sclerosis Society (http://www.nmss.org) in New York.
"Understanding the elements of the immunologic responsiveness to multiple sclerosis helps us in designing the kinds of therapies that are going to be needed to intervene in the immune process."
Reingold emphasized, however, that there are many factors that contribute to multiple sclerosis, and the complement system is one part of a larger disease process.
Journal of Immunology (1999:163)
December 14, 1999