By Merritt McKinney
NEW YORK, Apr 30 (Reuters Health) - Using "gene chips" that provide a snapshot of the activity of thousands of genes at once, scientists have identified new targets for drugs to treat multiple sclerosis (MS).
Based on the information gleaned from the gene chips, researchers were able to reduce the severity of the symptoms in mice with a similar degenerative neurological disease.
In MS, the slow destruction of myelin--the thin, protective coating that insulates nerve fibers in the brain and spine--can lead to numbness, muscle weakness and stiffness, impaired vision and coordination problems.
To see what role genes might play in the disease, Dr. Lawrence Steinman of Stanford University School of Medicine in California and colleagues used gene chips to take a look at gene expression--which genes are turned on or off--in MS-related brain lesions from four people who died from the disease.
Since inflammation plays a role in MS, it came as no big surprise that genes for several inflammatory molecules were expressed at higher levels in the brains of people who died of MS. But the researchers also found that gene expression was not the same in all MS lesions, according to the report published in the May issue of the journal Nature Medicine.
The next step for the investigators was to see whether they could use what they had learned about gene expression in MS to relieve symptoms of the disease. They worked with mice that were prone to develop experimental autoimmune encephalomyelitis, or EAE, a condition that also destroys myelin and that is used by researchers to mimic MS in mice.
In one experiment, the team discovered that one form of MS was less severe in mice with EAE who lacked one of the genes they found in MS. And mice lacking the gene did not develop another form of MS.
The next step, Steinman told Reuters Health, "will be to take some of the candidates revealed in these studies and to design therapies based on the insights."
The results "bring us closer to comprehending the mechanisms that contribute to MS," according to Drs. Stephen M. Tompkins and Stephen D. Miller at Northwestern University Medical School in Chicago, Illinois.
"The data may enable scientists to tailor therapeutic strategies" to different stages or forms of the disease, they suggest in an accompanying editorial.
But the editorialists caution against placing too much hope on the results in mice. "Clinical trials have shown that many therapies proven in the mouse have not been efficacious in humans," they write.
Several of the researchers work for Roche Bioscience in Palo Alto, California, which makes gene chips.
SOURCE: Nature Medicine 2002;8:451-453, 500-508.
Copyright © 2002 Reuters Limited