Researchers Unraveling Genetics of MS

Medical researchers have made significant progress in understanding the genetics involved in MS. In two new studies, published in the July 29th online edition of the New England Journal of Medicine and Nature Genetics, three teams of researchers say they have identified, by separate methods, new genetic variants that contribute to the disease.

The new research is the result of several large teams at universities in the U.S. and abroad who have coordinated their publications and pooled their data for analysis.

MS is a disease in which the body’s immune system mistakenly attacks myelin. For years, the cause of MS has been considered part genetic and part environmental. Trying to identify the genes involved, however, has proven frustrating. Consequently, researchers have been speculating about what genes might be involved and then seeing if individuals with MS have abnormal variants of that gene. In recent years, researchers have suspected more than 100 candidate genes, none of which could be confirmed, except for variations in the immune system that have been known about for some time.

One team used a new, advanced method called Whole Genome Association. The other teams used the candidate gene approach. Because all three teams identified the same gene, the researchers are confident they have opened a new avenue into the cause and possible treatment of MS.

The identified gene produces a substance called the interleukin-7 receptor, a protein that allows immune system cells to respond to a control agent. Researchers believe the receptor is part of a biochemical pathway involving many genes. Defects in any of these genes may lead to MS. Researchers now believe it is possible to explore the pathway and perhaps develop treatments to remedy the disease-causing process.

With these findings, researchers may be able to perform blood tests to identify people with the flawed genes and begin to develop drugs to counteract its effects.

One drug on the market, daclizumab (Zenapax), already works on interleukin-2 and is currently in a Phase II clinical trial exploring its potential use alone and in combination with other immune-modulating drugs in MS.

Unraveling the genetic mystery of MS is proving harder than other autoimmune diseases caused by one or two malfunctioning genes. MS appears to involve defects in many genes, each with only a modest effect. The newly identified defects, by themselves, raise the risk of MS by about 20 percent. The studies also found evidence that a dozen other genes may be linked to MS, providing future potential targets for MS researchers.

“It is important to realize that the increased risk contributed by these two genes is very low and only a small proportion of the variance in the risk of MS,” comments Jennie Lou, M.D. “People tend to get very excited when new genetic links are discovered but we need to keep in mind that the genetic picture of MS is still largely unknown – even with these significant studies.”