CHICAGO -- After decades of dead ends, scientists have identified two genes that might raise the risk of multiple sclerosis, providing insight into the causes of the debilitating disease.
The findings, released in two medical journals yesterday, describe the first genes conclusively linked to multiple sclerosis in more than 20 years, researchers said.
Multiple sclerosis is a disease of the central nervous system that affects about 350,000 people in the United States and more than 2.5 million globally.
In a large-scale study appearing in an online version of the New England Journal of Medicine, teams of international researchers scanned the entire human genome of more than 12,000 people for MS risk factors.
That study uncovered two new gene suspects, both of which are thought to play a role in autoimmune disease.
Researchers believe both environmental and genetic factors play a role in the development of MS, which attacks and destroys the insulation along nerve fibers.
Until now, the only genetic link identified with MS was the major histocompatibility complex, or MHC, a large cluster of genes essential to the immune system.
Neither of the newly discovered genes appears to be as instrumental to developing the disease as MHC, but the research is important because it provides insight into other genetic factors that raise the risk of developing MS.
"Having this genetic road map will be of incredible importance in developing new therapies," said Dr. David A. Hafler, a neurologist at Harvard Medical School and Brigham and Women's Hospital in Boston who worked on the genome study.
The role of one of the gene suspects in MS -- a variant of the interleukin-7 or IL-7 receptor -- was confirmed in two papers published online in Nature Genetics. The gene helps control the activity of regulatory T cells, which suppress the activation of the body's immune system.
"This discovery brings us into a whole new pathway that could have a very important role in understanding the fundamental mechanisms that trigger MS," said Dr. Stephen L. Hauser, professor of neurology at University of California, San Francisco, who worked on studies released online in the New England Journal of Medicine and Nature Genetics.
While the studies used different methods, they both pointed to IL-7.
The Nature Genetics study, led by Jonathan Haines of Vanderbilt University Medical Center, and Margaret Pericak-Vance of the University of Miami, examined variants in three genes. It found variants in IL-7 receptors were more common in MS patients than in healthy people.
The other gene identified by the whole genome scan -- the IL-2 receptor -- has been linked to two other autoimmune diseases: type 1 diabetes and autoimmune thyroid disease. "The story here is the commonality of autoimmune disease," Hafler said.
Many researchers trying to identify which genes are responsible for multiple sclerosis have been approaching the problem by guessing what genes might be involved and seeing whether patients have abnormal versions of those genes.
That approach has produced more than 100 possible candidates in recent years, but none could be confirmed except for the MHC genes, which help the immune system detect proteins that are foreign to the body.
One of the studies reported yesterday used a new method called whole genome association, which has produced several advances with major diseases in recent months. The other teams used the candidate gene approach, but all three teams identified the same gene and the researchers said they believe they have found a new path toward the cause and possible treatment of MS.
The teams conducting the research in the United States and abroad pooled their data and coordinated publication of their findings.
Researchers believe the interleukin-7 receptor is part of a biochemical pathway involving many genes that could lead to the disease. They say it is now possible to study that pathway further in the hope of developing treatments.
"This is a very good beginning," said neurologist Kari Stefansson of deCODE Genetics, a company based in Reykjavik, Iceland, that has spearheaded the hunt for genetic causes of common diseases.
The course of the disease is unpredictable, so clinical trials are difficult to conduct. "But once you have an ironclad discovery, as I believe the interleukin-7 receptor is, then you have the motivation to endure the expense of a long clinical trial," Stefansson said.
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