Solid evidence that best treatment for multiple sclerosis is pregnancy

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Solid evidence that best treatment for multiple sclerosis is pregnancyhttp://www.news-medical.net/?id=4375 Posted By: News-Medical in Medical Research NewsPublished: Friday, 27-Aug-2004 For years, doctors have suggested the best treatment for multiple sclerosis ispregnancy. Now, an Oregon study is delivering solid evidence to support the theory. Researchers at Oregon Health & Science University and the Portland Veterans Affairs MedicalCenter have uncovered the mechanism by which estrogen, produced in high volumes duringpregnancy, boosts the expression and number of regulatory cells that are key to fighting MSand other autoimmune diseases, such as arthritis and diabetes. The study, published in the "Cutting Edge" section of the current issue of The Journal ofImmunology, shows the hormone augments a compartment containing T cells known asCD4+CD25+, and a regulatory protein called FoxP3. The cells are important for protecting miceagainst a model for human MS called experimental autoimmune encephalomyelitis (EAE). Autoimmune disease has been associated with a deficiency of FoxP3, whose expression is areliable indicator of the regulatory T cells' function and development. "This is the first report that this single, benign compound – estrogen – can increase regulatorycells," said study co-author Halina Offner, Ph.D., professor of neurology, and anesthesiologyand peri-operative medicine, OHSU School of Medicine and the Portland VA Medical Center."When you remove (the CD4+CD25+ cells), animals get autoimmune disease. They're veryimportant to maintaining a healthy state." Dennis Bourdette, M.D., professor and chairman of neurology, OHSU School of Medicine, anddirector of OHSU's MS Center of Oregon, says understanding how estrogens boost protective Tcells to fight MS will lead to the development of "estrogen-like" drugs that could increase thecells without the female hormone's side effects. "Dr. Offner and her research team have made a major breakthrough in understanding howestrogens help MS," Bourdette said. "This breakthrough will provide a critical 'tool' for developing these new estrogen-like drugs." The study found that estrogen treatment simulates pregnancy in increasing T cell levels. It alsodemonstrated that estrogen boosts expression of the FoxP3 protein not only in a mouse model,but also in cell culture. "In vitro, estrogen can induce regulatory cells," Offner added. In their research, the OHSU-VAMC scientists saw a "significant increase" in the number ofCD4+CD25+ regulatory T cells – 43 percent – and a correlated boost in FoxP3 expression inmice treated for 14 days with estrogen versus untreated mice. Pregnancy increased theCD4+CD25+ count and amplified FoxP3 expression as well. Scientists have long been interested in the role sex hormones play in the body's ability to fightautoimmune diseases like MS, particularly since these disorders occur more frequently infemales than in males. But the link between pregnancy and MS has been hotly debated. In 1998, scientists in France went a step closer to putting the issue to rest when theyconducted the first large study aimed at assessing pregnancy and delivery on the course of thedisease. The group found there was a marked reduction in the rate of MS relapse duringpregnancy, especially in the third trimester. Three years later, Offner and a team of OHSU and Portland VA Medical Center neurologistspublished a study showing treatment with low doses of estrogen protects mice from developingEAE, but the mechanism of the effect hadn't been fully characterized. And earlier this year,researchers in the United Kingdom found that human pregnancy elevated levels of thedisease-fighting CD4+CD25+ T cells. However, "They didn't say it was (due to) estrogen," Offner said. Estrogen levels during pregnancy can be 50 to 100 times higher than normal, Offner said.Scientists attribute this jump to the body's natural defense against its own immune system,whose reaction to self-antigen proteins, or "self-Ags," in fetal tissue can lead to fetal rejection,as well as the chronic inflammation that is the root of autoimmune disease. "It's very well known that pregnant women are in remission. They do feel better," Offner said. "Ifyou could mimic pregnancy somehow, it would be great" as a therapy. Bourdette said many of his patients have told him their MS symptoms improved dramaticallyduring pregnancy. And a small clinical trial at the University of California, Los Angeles, showedestriol, the estrogen hormone produced during pregnancy and available as an oral therapy,showed "some benefit" for MS patients. "However, long-term estrogen therapy has potential side effects," and developing estrogen-likedrugs can help patients avoid these potentially detrimental effects, he said. Research is continuing on regulatory T cells – "T-regs," as they're often called – and theirpotential benefit for other autoimmune diseases, Offner said. "It would be nice to look at regulatory T cells in an animal model for arthritis," she said. "There'sstill a lot to do." The study was supported by grants from the National Institutes of Health, the National MultipleSclerosis Society, the MS Center Without Walls, the Department of VeteransAffairs, the American Diabetes Association and the Juvenile Diabetes Research Foundation. "Focus on what you do have and are able to do -- not on what you don't have or can't do." All of our support groups are listed below.For MS SupportMSers_Online For the support of the more serious issues dealing with MS.MSersSupportingMSers-subscribe This list is just to have "fun" and laugh. MSers_Online_Fun-subscribe Make New MS Friends!msersonlinefriends-subscribe This one is for Caregivers.For anyone who is a caregiver to a loved one.1_for_Caregivers-subscribe For Caregivers to get away and vent.caregivershideaway-subscribe Talk about all problems!MixedEmotions-subscribe Any questions? Please feel free to email me: ronpeg@...Take care! 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