Rutgers scientists help uncover protein implicated in multiple sclerosis

November 27, 2001

NEW BRUNSWICK/PISCATAWAY, N.J. - A team of investigators including Rutgers scientists has found an immune system protein normally protective against disease that appears to accelerate progression of multiple sclerosis (MS).

Finding out why the protein, osteopontin, helps rather than hinders MS could ultimately help scientists learn how to block MS, which damages communication among the brain's nerve cells by attacking the fatty myelin sheath that coats them. The research was reported in the Nov. 23, 2001 issue of the magazine Science.

Produced by many different cells in the body, osteopontin is found in all body fluids and is involved in the inflammatory response and appears to be required for moderating the response of the body to certain forms of infection and injury.

Osteopontin is a major focus of laboratory research at Rutgers and plays an important role in resistance to infection, according to Professor David T. Denhardt and Associate Research Professor Susan Rittling of Rutgers department of cell biology and neuroscience, two of the research paper's authors. "Take away osteopontin and you may be much more likely to die of some infection because your immune system has lost one of its key weapons," said Denhardt.

But when it comes to MS, osteopontin shows a negative side. Recent scientific investigations of MS have demonstrated that osteopontin is "expressed" or present in much higher levels in the brains of individuals with MS and in mice with a laboratory-produced "model" form of MS.

"What wasn't known was whether or not osteopontin's presence was simply incidental to MS and had nothing to do with the disease, or if it actually played a role in speeding up progression of the ailment," said Rittling.

To find out, the researchers used a "knockout" strain of mice developed at Rutgers -- mice whose genes do not make the protective protein osteopontin. Injected with another protein that causes the "model" MS, the mice without osteopontin were found to be resistant to the progression of the disease, according to Denhardt.

"Clearly, osteopontin does play a role in the progression of MS," he said. "If we can find out what it is doing, we may figure out a way to block that progression."

In addition to Rutgers' Denhardt and Rittling, the research team included lead investigators Dorothee Chabas of Stanford University and Sergio E. Baranzini of the University of California at San Francisco; Dennis Mitchell, Christopher Lock, Raymond A. Sobel, Jorge Oksenberg and Rosetta Pedotti of Stanford; Lawrence Steinman of the University of California at San Francisco; Marcela Karpuj of both Stanford and the University of California at San Francisco; Claude C. A. Bernard of La Trobe University in Australia, and Renu Heller of Roche Bioscience, Palo Alto, Calif.

Rutgers University

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