Scientists Block Multiple Sclerosis in Mice
Scientists have successfully blocked harmful, misdirected immune cells from reaching the brains of mice with a condition similar to multiple sclerosis. Results of the new study come from Washington University School of Medicine in St. Louis.
A mouse model may help with multiple sclerosis treatment
Multiple sclerosis is a chronic, often disabling autoimmune disease in which the body sends immune cells to attack the central nervous system (e.g., brain, optic nerves, spinal cord), and more specifically, the fatty sheath that protects the nerves called myelin. Symptoms can range from mild, such as numbness in the limbs, to severe, including paralysis or blindness, and also vary widely from patient to patient.
Efforts to better understand multiple sclerosis, its causes, and how it works have been underway, and this new study is one that called upon help from scientists at ChemoCentryx who are working on development of an anticancer drug. Researchers at Washington University used the anticancer drug to test their theories about immune cells in multiple sclerosis, and the results were “dramatic,” according to Robyn Klein, MD, PhD, associate professor of pathology and immunology, medicine, and neurobiology.
Klein noted that when they administered the drug to mice that had a multiple sclerosis-like condition, “the harmful immune cells were unable to gain access to the brain tissue, and the mice that received the highest dosage were protected from disease.”
The Washington University research team discovered the stairway immune cells must travel to reach the brain. Immune cells leave the bloodstream and enter the brain, crossing additional barriers and attack the myelin. The stairway is composed of molecules called CXCL12, which slow down the immune cells so they can be analyzed to determine if they are permitted to enter the brain tissue.
Klein discovered that multiple sclerosis causes CXCL12 to be moved out of the way, so no analysis takes place and the immune cells can move in and damage the myelin. The new drug, however, can block the removal of CXCL12 and thus prevent immune cells from entering the brain and doing damage.
Another lab informed Klein about a receptor called CXCR7, which binds to CXCL12. When the mice with multiple sclerosis were given the receptor, the immune cells were unable to get past the meninges (membranes that cover and protect the spinal cord and brain).
Klein made yet another discovery: immune factors could cause cells in the microvascular cells of the stairway to produce more or less CXCR7, which affects the number of steps on the stairway and thus the ability of the immune cells to reach the brain.
One question about multiple sclerosis has been why the disease can differ so widely from patient to patient. Klein noted that their new discoveries and “getting a better understanding of how these factors regulate immune cell entry will be an important part of answering that question.”