Multiple Sclerosis

Disease Background

Multiple sclerosis is an autoimmune disease that impairs the nervous system. In all autoimmune diseases, a person's immune system attacks the body, resulting in inflammation of various organs or tissues. The components of the immune system responsible for this effect are antibodies and cells. Antibodies, proteins produced by white blood cells, typically are made in response to infection caused by pathogens like bacteria and viruses. In autoimmune diseases, normal molecules of the body are mistakenly recognized by the immune system and targeted for destruction. In multiple sclerosis, the immune system specifically targets a protein called myelin, which coats nerve fibers.

Some patients with multiple sclerosis have severe symptoms, including paralysis, the inability to move or feel due to nerve damage, while others suffer only from mild weakness or numbness. Symptoms can be persistent or periodic and may also include loss of balance, tremors and loss of coordination.

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An estimated 400,000 people in the United States have been diagnosed with multiple sclerosis. Like other autoimmune diseases, multiple sclerosis occurs more frequently in women than men. A genetic component is suspected, since certain families have an increased predisposition to autoimmune diseases, although family members are not always afflicted with the same disease. The incidence of multiple sclerosis is higher in the most northern latitudes, suggesting there is an environmental component to the development of the disease. Researchers also suspect that a viral infection may trigger disease onset in genetically predisposed individuals.

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Our Research

Overview of Hutchinson Center Research

Center researchers are leading clinical trials that use stem-cell transplantation for treating severe forms of autoimmune diseases; a new trial for multiple sclerosis is expected to open in early 2006. Prior to the procedure, a patient's stem cells are collected, and cells that react against the patient's own tissue are removed. Next, patients are treated with high-dose chemotherapy and drugs to suppress their immune system. Patients then receive an infusion of the stem cells that were collected before treatment. These cells will rebuild a new, healthier immune system free of the self-reactive cells responsible for the autoimmune disease. Preliminary results from such studies have been promising.

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Uncovering the genetic secrets of autoimmune disease

The causes of autoimmune diseases, in which the immune system begins attacking the body's own tissues, are unknown. What triggers these diseases? How do they progress? Why do they strike women much more often than men? These form the core research questions of scientists in Dr. J. Lee Nelson's laboratory. Answering them requires a variety of approaches involving collaborations with laboratory, population and clinical scientists.

Nelson's laboratory studies focus on understanding the genetics that underlies the complex system by which the immune system distinguishes between the body's own cells and foreign invaders. Women with rheumatoid arthritis often experience a remission of symptoms during pregnancy, suggesting that incompatibility between the immune systems of mother and fetus may play a role in these diseases.

In collaboration with clinical researchers, Nelson's team is investigating the similarities of scleroderma and chronic graft-vs.-host disease. Graft-vs.-host disease results from an incompatibility of the donor's immune cells and the patient's tissues. Nelson's team has shown that persistent fetal immune system cells in the mother's blood are quantitatively greater in women with scleroderma compared to healthy women. More recently, they showed that among the cell-surface proteins that form the identification system of the immune system, those produced with certain characteristics called human leukocyte antigen (HLA-DRB1) were associated with increased risk of subsequent scleroderma in mothers studied.

Determining the role of genetic predisposition and environmental factors involves collaborating with population scientists in the Hutchinson Center. Nelson's studies have shown that immune cell incompatibility can apply to men and women who have not been pregnant because incompatible cells can engraft from a twin or from a blood transfusion. More recently her team found that cells from a mother can persist in her children into adult life.

See also the Dr. Nelson's Web site.

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Innovative new treatments for autoimmune diseases

A Hutchinson Center study, led by Dr. Richard Nash, is examining the feasibility of using stem-cell transplantation as a treatment for autoimmune diseases. These diseases are a group of about 50 ailments whose symptoms range from mild rashes to life-threatening conditions that attack major organ systems. Though each disease is different, all begin with an immune-system malfunction: destruction of the body's own normal tissue by cells that typically fight infections caused by bacteria, viruses and other micro-organisms.

The rationale for the approach is that the high-dose radiation and chemotherapy is used to wipe out cancers of blood and bone marrow may be used to suppress the immune system. This high-dose therapy eliminates not only the immune system's ability to fight infection, but also its ability to attack the patient's tissues. The new immune system that regrows from selected stem cells taken from the patient's own blood will be composed of immature cells that will not include the reactive cells that trigger the immune system to attack the body. Because many autoimmune diseases begin during middle age, it is thought this stem-cell transplantation will "turn back the clock" on immune system development in these patients.

The early phase studies showed that transplantation provides promising improvement in patients' conditions, and that larger randomized comparison studies are needed to determine the long-term benefit to patients.

For more information, Search Clinical Trials.

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Relevant Articles

• From basic discovery to breakthrough drug — 'Determination and persistence' carries a controversial theory to development of drug that prevents inflammation, reduces MS relapse
  
  
• Best hope may lie in vulnerability — Nash lab pioneers use of transplants to fight autoimmune disease

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