April 3, 2000
Volume 52, No. 27
Study sheds new light on multiple sclerosis
By Holly Korschun
Scientists at the School of Medicine have uncovered a significant connection between mast cells--a type of immune cell--and the development of multiple sclerosis (MS), an autoimmune disease that attacks the central nervous system.
Until now, research into the mechanisms of MS has focused almost exclusively on errant responses by immune T-cells that attack the body's own tissues. The new discovery, made in a mouse model of MS that is very similar to the human form of the disease, provides a new perspective on how the disease does its damages.
The finding holds particular significance because extensive research already has led to the development of drugs that effectively block the action of mast cells in other diseases. The Emory team's discovery was reported in the March 5 Journal of Experimental Medicine.
In MS, genetic and/or environmental factors are thought to cause the immune system to mistakenly attack the protective myelin sheath that insulates nerve cells. This results in patchy scarring, or plaques, that impair communication throughout the central nervous system.
Although not fatal, MS causes progressively debilitating symptoms in many of its victims, decreasing life expectancy by an average of six years. Problems include weakness, numbness, infections and difficulty performing mental tasks. There is no cure for the disease, and only a few drugs can slow its progression. It affects approximately 1.1 million people worldwide, including nearly 350,000 Americans. Symptoms usually begin between 15 and 40 years of age.
Pathologist Melissa Brown and Ginny Secor, a doctoral student in Brown's laboratory, pieced together several parts of a research puzzle to develop their hypothesis that mast cells are linked to MS. Brown's earlier work focused on the regulation of cytokine gene expression in T- and mast cells. Cytokines are proteins that act to orchestrate signals between immune cells. The investigators first realized that many of the cytokines implicated in MS are produced by mast cells.
Next they uncovered little-known research showing that mast cells are prevalent in the central nervous system. Believing that mast cells might play a key role in MS development, Brown and Secor tested their hypothesis using a type of mutant mouse deficient in the cells. They injected myelin proteins designed to induce the mouse counterpart of MS, a disease called experimental allergic encephalo-myelitis (EAE). The mice exhibited significantly reduced disease incidence and delayed disease onset as compared to control animals.
"Clinicians and most researchers have not seriously considered the potential role of mast cells in multiple sclerosis, so we are particularly excited about these findings," said Brown "especially because mast cells have been well studied in the respiratory tract and the skin as effector cells in hay fever, asthma and atopic dermatitis. In allergy and asthma, compounds such as cromolyn sodium antihistamines have been developed that can either block the release of mast cell mediators or block their activity."
Brown said a big question remains as to whether drugs already used to treat respiratory tract diseases such as allergies and asthma would be effective in treating MS or would need to be modified in order to gain entry into the central nervous system.