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Pneumonia, MS link investigated

BY: NANCY HUMPHREY

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4/23/1999 - Dr. Subramaniam Sriram is probing the relationship between certain pneumonias and multiple sclerosis. (photo by Donna Jones Bailey)

Researchers in the Vanderbilt Multiple Sclerosis Center are exploring the relationship between a common organism responsible for community-acquired pneumonias and Multiple Sclerosis.

The Vanderbilt research focuses on the role of Chlamydia pneumoniae, also known as C. pneumoniae, believed to be the cause of 20 to 30 percent of cases of pneumonia in a community setting, in the development of MS.

"The idea that infection may be a cause of MS is not a new theory and stems from the fact that an environmental cause of the disease has been known by a number of indirect evidences," said Dr. Subramaniam Sriram, William C. Weaver Professor of Experimental Neurology and director of the Multiple Sclerosis Center.

Sriram will present his findings on April 23 at the American Academy of Neurology meeting in Toronto.

Previously, researchers have looked at a virus as the infectious agent that may cause MS.

"That has never panned out," Sriram said. "The clinical and pathologic presentation is one of a chronic infection. That's why we come back to an infectious cause over and over again."

The new theory is that Chlamydia, a relatively newly discovered organism, may act as a trigger toward the development of MS, Sriram said.

The Vanderbilt research team began to look at Chlamydia two years ago when Sriram saw a patient with MS who had failed non-conventional immunosuppressive and immunomodulatory therapies.

Following discussions with Drs. Charles W. Stratton, associate professor of Pathology, and William M. Mitchell, professor of Pathology, he decided to explore the chance that a Chlamydia agent might be responsible for MS.

"We explored this in this one gentleman and were successful in culturing the organism," Sriram said. "He subsequently made a fairly dramatic recovery from his MS with long-term antibiotic therapy."

However, Sriram said it is too early to make the assumption that the antibiotics made a difference in the man's illness.

"Extreme caution should be exercised in making causal associations between anecdotal success and what the disease does as part of its natural course. Since MS is known for its spontaneous remissions it is difficult to conclude in one patient that the antibiotics he received was responsible for his recovery. However, in his case, the improvement was so dramatic that we decided to explore the issue further."

Armed with a pilot grant from the National Multiple Sclerosis Society, the Vanderbilt research team has studied a more extensive group of patients over the past two years. The organism was found in the central nervous system of a majority (90 to 95 percent) of the MS patients who were tested.

Evidence from a number of angles points to the presence of Chlamydia, Sriram said.

"This observation is interesting and is breaking new ground for a number of reasons," Sriram said. "Even when other associations with viral organisms have been entertained, the degree of association has never been so high as with Chlamydia pneumoniae. We can demonstrate the evidence by a number of means - by culture, or by PCR techniques -- that show there are antibodies to this organism present in the spinal fluid of these patients," he said.

The Vanderbilt research has also shown that the organism is present early in the disease course and appears to persist.

The next step is a larger study, sponsored by the National MS Society, to be conducted over a three-year span.

"We will be studying 50 patients and prospectively following them over three years," Sriram said. "We will be looking at the brains of MS patients who have died from the disease or in whom a brain biopsy was done to show the presence of the organism," he said, adding that preliminary evidence in autopsies of MS patients who have died from other causes shows the organism can be detected in the brain.

About one-half million people in the United States have MS. There are about 2,000 patients in the Middle Tennessee area. About 1,200 of those patients are seen at the Vanderbilt center.

Sriram said the research may show that Chlamydia may not be directly responsible for the disease.

"Many people believe MS is an autoimmune disease and that the organism may initiate an immune response that goes ahead and does the damage although the organism itself does not secrete any toxin or harmful compounds. The disease may be the inadvertent injury in the body's attempt to get rid of the organism."

Sriram said he is "cautiously optimistic" about what answers the research may provide.

"It's just too early to say," he said. "Given the fact that the history of an infectious etiology has been very difficult to prove in the past, and prior organisms that were entertained as potential candidates have not been proven to be the cause, enormous caution needs to be exercised in showing the relationship between the organism and the disease before Chlamydia pneumoniae can be directly implicated as a causative agent in MS."

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