Researchers have uncovered new genetic variations that appear to put one at increased risk for multiple sclerosis, in a discovery that's being called the first real progress on the genetics of MS in 30 years.

The finding is the result of a huge, international research collaboration that sought the genetic basis of MS, an autoimmune disease of the central nervous system in which the body attacks and destroys the insulation along nerve fibres. It leads to symptoms ranging from mild muscle weakness to paralysis.

It's long been suspected that MS arises from a combination of genetic and environmental factors. But the genetic source has remained mostly a mystery.

Unlike diseases caused by a mutation in a single gene, MS appears to be among a list of complicated diseases in which a host of genetic variations contributes to a person's susceptibility, with each gene contributing only a small amount of risk.

The only genetic link previously identified is in the major histocompatibility complex (MHC), a large cluster of genes responsible for many immune functions, including preventing the body's immune cells from attacking its own tissues.

This latest research, which analyzed genomic information from 12,360 people, confirmed that link but went further.

The researchers gathered 931 sets of DNA samples from MS patients and their parents. They analyzed single nucleotide polymorphisms (SNPs) -- that is: those small differences in DNA sequence that represent the most common genetic variations between individuals. They then looked for variations that were more commonly inherited by people with MS compared to samples from people without the disease.

To double-check the findings, they performed a second analysis of other sets of families, individual cases of MS, and a control group. In the end, all the samples were combined for a final analysis of more than 12,000 subjects.

What they found was that one of the genetic regions that are more common in people with MS contains a gene called the IL-2 receptor, which has also been linked to two other autoimmune diseases: type 1 diabetes and autoimmune thyroid disease.

David Hafler, a neurology professor at Harvard Medical School and one of the study's authors says this study will likely spur further research into the connection between these seemingly separate conditions.

Another region contains a gene called the IL-7 receptor, which helps to control the activity of a class of immune cells called regulatory T cells.

Two papers appearing simultaneously in Nature Genetics confirm this finding, and explore how the change in the IL-7 receptor affects the immune system. One of the authors of the study says that the IL-7 receptor will now become a major focus of research on MS.

"One of the most encouraging outcomes of this current genomic study," says Dr. John Richert, Executive Vice President, Research & Clinical Programs, National MS Society, "is that it is helping us to pinpoint genes that may elevate the risk of developing MS and other autoimmune diseases, pointing the way to new areas of research and new therapeutic targets to both treat and eventually prevent these diseases."

"People have been looking for genes involved in MS for 30 years," Hafler says. "Why weren't they found? The answer is you couldn't do it without the sequence of the human genome."

The next step, Hafler said, is to begin to collect larger numbers of samples and examine more DNA sequences, which will allow scientists to identify subtler variations that contribute to the disease.

CTV's medical consultant Dr. Marla Shapiro said while the study won't likely lead to any immediate advancements in treating MS, but it will lead to greater understanding of the disease. Shapiro said it will help scientists with questions such as:

  • Why do some people who have MS have a benign course and others have a much more aggressive course?
  • Can we predict the disease by knowing the genetics and therefore know how to treat them more accurately?
  • Can we predict who will be at risk; and
  • Ultimately, will we be able to develop a screening test?

"So by understanding the mechanism behind this disease that is likely the interplay of lots of genes as well as the environment, it gives us new hope for preventing, for curing, and for treating more effectively," said Shapiro.