http://globalarchive.ft.com/globalarchive/article.html?id=020430010220&query=sclerosis

April 30, 2002
Business Wire
News & Medical Writers
STANFORD, Calif
BW HealthWire

Using microarray technology, researchers at Stanford University Medical Center have uncovered thousands of genes that may be involved in multiple sclerosis

Although some of the genes are new, others were known genes that had previously been thought to play roles that were unrelated to MS

These results could lead to new treatments and help clarify previous observations about the disease

"We've been bumping around looking at a few genes," said Lawrence Steinman, MD, professor of neurology and neurological sciences

"Now there are hundreds if not thousands of other genes that may be critical." This work will be published in the May issue of Nature Medicine

MS occurs when cells of the immune system target their attack on cells that insulate neurons in the brain

The disease generally progresses in stages with an acute attack followed by a recovery - or chronic phase - in which the insulating cells degenerate and scar tissue builds up

Eventually, the disease can lead to paralysis and sensory disturbances such as blindness or deafness

Steinman looked at which genes were being expressed in both acute and chronic attacks and compared them with the genes active in normal brain tissue

To do this, Steinman's team isolated messenger RNA from acute, chronic and normal brain samples (mRNA is produced by active genes and can be used to identify which genes are being expressed in a given sample)

They then exposed the mRNA samples to a gene chip - a glass slide dotted with human genes

If a sample contained mRNA corresponding to a gene on the chip, it would bind to the spot and produce a visible signal

The bigger the signal, the more mRNA, and therefore the more actively the gene is expressed in the sample

With this technique, Steinman picked out thousands of genes that were expressed at either higher or lower levels in MS compared to the normal brain sample

Some of these genes were exactly what Steinman would have predicted, including the immune-stimulating factors called cytokines

"We would expect to see angry, inflammatory cytokines in acute MS and scarring in chronic MS, and indeed that's what we did find," he said

But he also had some surprises

Steinman found genes expressed at high levels that had previously been found only in bones, in allergic responses and in pregnancy

He said that with only 30,000 genes to work with, the body may reuse genes for many roles

"Multiple purposes may be the rule," he said

He expects that future gene-chip experiments will turn up additional known genes playing previously unknown roles

Some of the unexpected proteins Steinman found may help resolve previous observations about MS treatment

In the past, people have found that both pregnancy and allergy can prevent MS, he said, but nobody understood why

Among the genes that were overexpressed was a histamine receptor and proteins associated with pregnancy

These results could lead to the regular use of antihistamines to treat MS

"It sure is easier to start with a drug that's approved for over-the-counter use," Steinman said

He also intends to test novel proteins for use in preventing MS

To verify that proteins found in this study could lead to possible cures, Steinman tested two treatments in a mouse model

In one, he created a mouse line that was prone to developing MS but lacked a gene that was overexpressed in chronic MS

These mice had fewer signs of the disease during the chronic phase than the MS-prone mice that still had the overexpressed gene

He also injected MS-prone mice with a protein found in the acute phase of the disease and saw a delay in the onset of MS in the mice

The complete list of genes that are overexpressed or underexpressed in acute and chronic MS will be published online in conjunction with the paper

Steinman hopes other researchers will scrutinize this list and devise their own novel treatment strategies

"There will be a lot of people who might mine this data for real nuggets," he said

Primary authors on the paper include Stanford postdoctoral researchers Christopher Lock, MD, PhD; Guy Hermans, PhD; Rosetta Pedotti, MD; and Andrea Brendolan, MD

The research was done in full collaboration with Renu Heller, PhD, at Roche Biosciences, who was instrumental in developing microarrays for analyzing tissue from human diseases

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital

For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu .

CONTACT:

Stanford University Medical Center
Amy Adams, 650/723-3900 (MEDIA)
or
BROADCAST MEDIA:
M.A. Malone, 650/723-6912
 

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