Scientists Block Immune Cells From Brain, Prevents MS Symptoms

Scientists from the Washington University School of Medicine in St. Louis have successfully blocked immune cells from entering the brain in mice suffering from a condition similar to multiple sclerosis. The researchers believed this to be a valuable breakthrough in the fight against MS. The study also introduced a possible compound currently in development for treating cancer that may also be used to someday treat MS.

MS is a condition that is characterized by the body’s immune cells being misdirected to attack the cells in the brain as well as the myelin sheath that insulates the neurons that conduct nerve impulses. But immune cells need to enter into the brain in order to do its damage. The researchers recently found out about a chemical stairway that is used by the immune cells in order to climb and gain entry into brain tissue.

The said chemical stairway is found in the tissue side of the microvasculature, small microscopic vessels that transport blood into the central nervous system. The steps of the so-called stairs are made up of a molecule called CXCL12. This molecule functions to regulate and evaluate immune cells to determine if they can be allowed to enter into the brain.

The researchers found that MS causes the CXCL12 molecule to be pulled inside the blood vessel cells in humans as well as in mice. This effectively removes the steps of the chemical stairway as well as the checkpoint function that the molecule provides. The researchers showed that by blocking the molecule from being pulled inside the blood vessel cells prevented the immune cells from entering and doing its damage in the brain.

Another separate study also brought to the attention of the researchers the molecule called CXCR7, a receptor that also binds to CXCL12. Both of these molecules are known to have been produced by the same cells in the microvasculature. The researchers have seen the receptor take copies of CXCL12 and the dump them into the lysosomes of the cells, pockets where molecules that the cell no longer needs are broken down and recycled.

According to Robyn Klein, MD, PhD, associate professor of pathology and immunology, of medicine and of neurobiology, “After it dumps its cargo in the lysosome, the receptor can go right back to the cell surface to pull in another copy of CXCL12.”

“There likely exists an equilibrium between expression and disposal of CXCL12. Some of the proteins expressed by the immune cells in MS patients affect CXCR7 expression and activity, disrupting the equilibrium and stripping the steps from this immune cell stairway we’re studying,” Klein further added.

The researchers then approached scientists at ChemoCentryx, a company that was developing a blocker for the CXCR7 receptor for cancer treatment. When the said blocker was given to a mice suffering from a condition closely similar to MS, the immune cells were effectively prevented from entering into brain tissue and causing damage to myelin. This study may have provided researchers with a better insight that will make them understand the said autoimmune disease in a better light.

“One of the biggest questions in MS has been why the location, severity and progression of disease varies so much from patient to patient,” Klein stated. “Getting a better understanding of how these factors regulate immune cell entry will be an important part of answering that question.”

Source: Washington University School of Medicine in St. Louis. “Multiple sclerosis blocked in mouse model: Barring immune cells from brain prevents symptoms.” ScienceDaily 7 March 2011. 15 March 2011 <http://www.sciencedaily.comĀ­/releases/2011/03/110307103652.htm>

 
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