http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2001/11/23/MN170096.DTL

Friday, November 23, 2001
Carl T. Hall, Chronicle Science Writer

Scientists have discovered genes that may help explain why some early cases of multiple sclerosis progress to a devastating form of the disease while others do not.

Researchers at Stanford University and the University of California at San Francisco are reporting a long list of genes found to be active in the brains of people with MS, a chronic autoimmune disorder in which nerve fibers lose their insulating sheaths.

The study, appearing today in the journal Science, found 300 to 400 genes active to some degree, including 54 "MS-specific" genes that were highly active. Several of these had not previously been associated with MS, and a few novel genes have no known function, or even a name.

Researchers focused special attention on a single gene known to be involved in inflammation and immune function, which is thought to be a key culprit in MS.

That gene produces a substance called osteopontin that was found to be overproduced near sites of damage to nerve cells, based on analysis of autopsy tissue samples. Further analysis in mice suggested that osteopontin plays a big role in shaping the course of MS and severity of symptoms.

Osteopontin, known to play a role in healthy bone formation, had not been implicated in MS until now. Dr. Larry Steinman, a Stanford neurologist and senior author of the study, said the protein appears to serve as "a very important switch" in the nervous system of MS patients.

NEW TARGET FOR TREATMENT

That raises the possibility of a new target for treating the disease, if a reliable way can be found to reduce the unwanted osteopontin without creating intolerable side effects.

Clinicians said the research is an important but early step toward getting a handle on an unpredictable disease that affects about 350,000 people in the United States, most often women in their 20s and 30s.

"It tells us about the mechanism of the disease, but this is only one element," said Dr. Mark Agius, director of an MS clinic at the University of California at Davis.

SEEKING BETTER DIAGNOSTIC TOOLS

"It's not the answer to MS, it's not the cause of MS, but the importance is that it identifies one key step, among many important steps, in the disease process," he said.

Dr. John Schafer, neurologist at MedClinic in Sacramento, a multispecialty clinic in the Catholic Healthcare West system, said physicians are in desperate search of better diagnostic tools, especially in the early stages when key treatment decisions have to be made.

Although there is no cure for MS, some drugs can be used to reduce symptoms and perhaps slow disease progression, but the drugs are expensive and can have side effects.

"The stakes are fairly high," Schafer said. "We can't tell very well in the early stages who's going to do well and who's not."

Along with Steinman, researchers included Jorge Oksenberg, a former post- doctoral fellow with Steinman at Stanford and now a UCSF associate professor of neurology. Lead authors of the study were Dorthee Chabas and Sergio Baranzini, who at the time were post-doctoral fellows at Stanford and UCSF, respectively.
 

©2001 San Francisco Chronicle