Promising Diagnostic Tools for Multiple Sclerosis Developed at Yale
|Antibodies that contribute to mouse disease similar to multiple sclerosis bind to oligodendrocytes, the cells that make myelin|
Yale School of Medicine researchers, in collaboration with the University of Connecticut Health Center, have identified three rapid diagnostic methods that can target antibodies commonly found in multiple sclerosis (MS) patients, greatly improving potential diagnosis and treatment.
The team reports their findings in this week’s Proceedings of the National Academies of Science. MS is a crippling neurological disease resulting from damage to myelin insulation surrounding nerve fibers, and to nerve fibers themselves. MS symptoms can include muscle weakness or paralysis, loss of vision, loss of coordination, fatigue, pain and memory loss. There is currently no cure for MS. Existing medications and treatments help manage symptoms, slow down or modify disease progression.
Although anti-myelin antibodies are often found in MS patients, the diagnostic value of these molecules that respond to infection are limited because they are also found in patients without MS, making it difficult to determine their role in the development of the disease. In addition, MS patients might generate anti-myelin antibody responses that reflect, rather than cause, the disease.
To address this diagnostic challenge, Nancy H. Ruddle, the John Rodman Paul Professor of Epidemiology and Public Health and Immunobiology at Yale School of Medicine, and her team developed mouse models to find ways to distinguish between antibodies that cause MS from those that are present in MS patients but do not cause disease symptoms.
The team, including researchers from the University of Connecticut, developed two ways to induce MS symptoms in mice. They found that though both treatment procedures yield antibodies to myelin, only one method made antibodies that could cause disease in other mice. These antibodies were shown to recognize and interact with a form of modified myelin found in MS. This myelin was not recognized with the antibodies that did not cause disease.
“Our results bring us one step closer to pinpointing more accurate diagnostic tools to aid in designing treatments for individual MS patients,” said Ruddle, who is also Interim Deputy Dean and Interim Vice Chair of Epidemiology and Public Health at Yale.
Other authors on the study include first author Cecilia B. Marta, Alfred R. Oliver, Rebecca A. Sweet and Steve E. Pfeiffer.
PNAS 102: online week of September 19, 2005; in print on October 4, 2005