Description: Reporting in the May 15 Journal of Clinical Investigation, VA scientists have found that a combination of estrogen and a T cell receptor vaccine completely prevents a disease resembling MS in female mice.
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Joel Preston Smith
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ESTROGEN AND VACCINE COMBO MAY STOP MULTIPLE SCLEROSIS
PORTLAND, OR.-- A new study by U.S. Department of Veterans Affairs (VA) researchers offers potentially good news for women suffering from multiple sclerosis (MS) and other "autoimmune" diseases in which the immune system mistakenly attacks the body's own tissues.
Reporting in the May 15 issue of the Journal of Clinical Investigation, VA scientists have found that a combination of estrogen and a T cell receptor (TCR) vaccine completely prevents a disease resembling MS in female mice.
Female mice treated with either the TCR vaccine or estrogen alone developed fewer symptoms of the MS-like disease than mice getting no treatment, the researchers found.
"But when we used combined therapy, the animals were completely protected and didn't become even mildly ill," said first author Halina Offner, Ph.D., co-director of the Neuroimmunology Research Program at the Portland VA Medical Center and professor of neurology at Oregon Health Sciences University (OHSU).
"We were really struck by the power of putting these two therapies together," said co-author Arthur Vandenbark, Ph.D., VA senior career scientist and OHSU professor of molecular microbiology, immunology and neurology.
Estrogen may also offer potential in combination treatments for other autoimmune diseases, Offner said. These disorders, such as rheumatoid arthritis and Grave's disease, are much more common in women than in men. Multiple sclerosis afflicts some 350,000 Americans and is caused in part by white blood cells that attack the myelin sheath surrounding nerves.
Resultant inflammation and scarring interfere with nerve function, leading to symptoms such as muscle weakness, fatigue, numbness and loss of balance. MS episodes usually worsen over time, and many patients end up in wheelchairs.
In a search for more effective treatment, the Portland VA/OSHU team developed a TCR vaccine to block certain receptors -- cellular docking sites -- on the surface of the errant white blood cells, preventing them from interacting with myelin. The vaccine also works by boosting numbers of regulatory T cells that keep the errant T cells in check. In clinical studies, TCR vaccine treatments have helped slow progression or improve symptoms in some patients with MS, but the researchers have been investigating ways to improve its potency.
Physicians have long noted that women with MS go into remission during pregnancy, Offner pointed out. Mice with the similar disease also improve during estrus and pregnancy, when estrogen levels are high. "This pointed us in the direction of estrogen," Offner said. The Portland VA/OSHU team subsequently showed that the myelin-attacking T cells bore receptors for estrogen, suggesting that estrogen could interact with the cells.
In the new study, the researchers compared groups of mice that would develop the MS-like disease if untreated. Groups included untreated males and females, males treated with TCR vaccine alone, females treated with estrogen or TCR vaccine alone, and females treated with both estrogen and vaccine.
As expected, all untreated mice developed full-blown cases of the MS-like disease. Vaccine alone prevented the disorder more effectively in males than in females, and only the estrogen-vaccine combination completely protected females. In addition to boosting numbers of regulatory T cells, the researchers found combination therapy increased levels of proteins that reduce inflammation. The mice were followed for 30 days.
The researchers don't know whether their promising results can be repeated in humans, Offner cautioned. In addition to pursuing the possibility of trials in MS patients, researchers plan further studies looking at estrogen's potential to augment other types of immune system therapies.
Other co-authors of the Journal of Clinical Investigation paper include Kirsten Adlard and Alex Zamora at the Portland VA Medical Center. The work was supported by VA, the National Institutes of Health, National Multiple Sclerosis Society, and the Nancy Davis Center Without Walls.
VA research provides improved medical care for veterans, as well as the general population. Through its unique affiliation with medical schools, VA plays a crucial role in educating future physicians in research and clinically oriented areas.
SPECIAL NOTE FOR REPORTERS: Dr. Halina Offner of the Portland VA Medical
Center and first author of the Estrogen/TCR Vaccine Combo study, is available
for press interviews to discuss the details of this new research. For telephone
or on-site interviews, please contact Joel Preston Smith at (503) 220-8262,
ext. 55084 or Patricia Forsyth at (503) 402-2975. For additional assistance,
please contact Jim Blue at (212) 807-3429.