An international team of researchers have identified some of the molecules that lead to inflammation of the brain among multiple sclerosis patients, according to a study published in this month's issue of The Journal of Clinical Investigation. The finding suggests that MS could be treated by blocking the cell receptors for those molecules.
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RESEARCHERS IDENTIFY MOLECULES INVOLVED IN MS INFLAMMATION
Study raises hopes that MS could be treated by blocking chemokine receptors
An international team of researchers have identified some of the molecules that lead to inflammation of the brain among multiple sclerosis patients, according to a study published in this month's issue of The Journal of Clinical Investigation. The finding suggests that MS could be treated by blocking the cell receptors for those molecules, similar to treatments currently being developed for diseases as diverse as asthma and AIDS.
"Multiple sclerosis is a disease in which white blood cells invade the brain and the resulting inflammation injures the central nervous system. To stop this inflammation, we need a better understanding of the molecular details behind this process", said the study's lead author, Richard M. Ransohoff, M.D., a neuroscientist at the Cleveland Clinic's Lerner Research Institute and the Mellen Center for Multiple Sclerosis Treatment and Research.
Researchers from the Lerner Research Institute, the University of Copenhagen in Denmark, the Mayo Clinic and the University of Michigan Medical Center studied molecules called chemokines, which attract the white blood cells. They identified two chemokines and two receptors that appear to be associated with the active disease in MS patients.
The chemokines are produced by cells in the central nervous system. The receptors are found on white blood cells that are attracted to the chemokines and travel in the blood to the origin of chemokine production. The clustering of white blood cells at the source of specific chemokine production is a critical factor in inflammation of the nervous system.
"These chemokines are like honey to the bee. The chemokines are secreted from cells and get caught up in the matter surrounding the nervous system cells. Certain white blood cells seek out the chemokines. These cells include the orchestrators of inflammation, activated T-cells, and macrophages, their major henchmen in the inflammation of MS. White blood cell chemokine receptors bind to the chemokines, and the cells then take up residence at sites of inflammation in the nervous system", said Dr. Ransohoff. "While these white blood cells are normally an important part of our immune system, they become destructive in people with MS."
Researchers have studied the role of chemokines in other diseases, such as rheumatoid arthritis and asthma, but this was the first in-depth study examining their role in MS.
Now that the individual chemokines and receptors have been identified, Dr. Ransohoff said, the next step is to develop molecules that block receptors on white blood cells so that those cells fail to migrate to the nervous system source of chemokines. Since recent studies have documented a direct correlation between inflammation in the central nervous system and the progression of MS, blocking these cells could have a profound impact on the disease, said Dr. Ransohoff.
Receptor blocking research is currently underway for other diseases, such as AIDS. MS researchers could build on that work to develop a treatment for MS, Dr. Ransohoff said.
"With many diseases, we can treat only the symptoms. To truly stop these diseases, we must combat them on the molecular level", said Dr. Ransohoff. "This study lays the foundation for a new generation of treatments for multiple sclerosis."
About 350,000 Americans have been diagnosed with multiple sclerosis. It can strike at almost any age but is most common among people in their 20s and 30s. In fact, it is the leading cause of nontraumatic neurological disability among young adults in North American. Women are almost twice as likely to be diagnosed with MS than men.
The Cleveland Clinic, through the Department of Neurosciences and the Mellen Center for Multiple Sclerosis, maintains one of the country's largest programs for the MS treatment and research.
The Cleveland Clinic Foundation, founded in 1921, integrates clinical and hospital care with research and education in a private, non-profit group practice. Last year at the Cleveland Clinic and Cleveland Clinic Florida, over 850 full-time salaried physicians representing more than 100 medical specialties and subspecialties provided for 1,182,300 outpatient visits and 49,987 hospital admissions for patients from throughout the United States and more than 80 countries. In 1997, the Cleveland Clinic Health System C comprising The Cleveland Clinic Foundation and Euclid, Fairview, Health Hill, Hillcrest, Huron, Lakewood, Lutheran, Marymount, and South Pointe hospitals C was formed. With 2,957 staffed beds, the Cleveland Clinic Health System offers broad geographic coverage, a full continuum of care, improved quality and lower cost of care to Northeast Ohio residents.
The Cleveland Clinic's website address is: http://www.ccf.org