July 30, 2007
Advances Cited in Research on Multiple Sclerosis
By NICHOLAS WADE
Medical researchers have made a significant advance in understanding
multiple sclerosis, a common neurological disease that causes symptoms
ranging from muscle weakness to paralysis.
The disease is one in which the body's immune system mistakenly attacks
the electrical insulation of nerve fibers. The cause is part genetic and
part environmental, but researchers trying to identify the relevant
genes have endured repeated frustration. Their approach has been to
guess what genes might be involved and see if patients have abnormal
versions.
This guesswork has produced more than 100 candidate genes in recent
years, none of which could be confirmed except for long-known variants
in the mechanism used by the immune system to recognize proteins that
are foreign to the body.
In three articles published online yesterday in The New England Journal
of Medicine, three teams of researchers say they have identified, by
separate routes, new genetic variants that contribute to the disease.
One team used a new, advanced gene-hunting method called Whole Genome
Association, which has racked up a string of successes with major
diseases in the last few months. The other teams used the candidate gene
approach, but because all three teams identified the same gene, the
researchers say they are confident they have opened a new window into
the cause and possible treatment of multiple sclerosis.
The gene makes a substance called the interleukin-7 receptor, a protein
that enables cells of the immune system 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 the
disease. It is now possible to explore the pathway, they say, in the
hope of devising treatments to correct the disease-causing process.
The new research is the product of several large teams at universities
in the United States and abroad who have coordinated their publications
and pooled their data for analysis.
The leaders of the Whole Genome Association Study include David A.
Hafler of Brigham and Women's Hospital in Boston; Stephen L. Hauser of
the University of California, San Francisco; and Jonathan L. Haines of
Vanderbilt University Medical Center in Nashville. The two candidate
gene studies were headed by Dr. Haines and Jan Hillert of the Karolinska
Institute in Stockholm.
Because the course of the disease is unpredictable, clinical trials are
hard to conduct, said Dr. Kári Stefánsson, chief executive of Decode
Genetics in Reykjavik, Iceland. "But once you have an ironclad
discovery, as I believe the interleukin-7 receptor is," Dr. Stefánsson
said, "then you have the motivation to endure the expense of a long
clinical trial."