http://www.yaledailynews.com/article.asp?AID=30043

BY REBECCA YERGIN
Contributing Reporter

Each year around 2.5 million people world-wide, including 400,000 Americans, are affected by multiple sclerosis, a crippling disease that targets the brain and spinal cord. While the exact causes for this disease remain unknown, recent research by the Yale School of Medicine and the University of Connecticut Health Center brings scientists one step closer to finding a cure.

The study, co-authored by Nancy Ruddle, director of graduate studies for epidemiology and public health at Yale, and University of Connecticut professor Stephen Pfeiffer, was published in last week's "Proceedings of the National Academies of Science." The team was successful in distinguishing between antibodies that do and do not contribute to the disease, but the two researchers said there is a long way to go before multiple sclerosis can be fully understood and prevented.

"Research like this is a little piece to a larger puzzle," Pfeiffer said. "[Finding a treatment] will not happen in one big flash. A treatment will be the development of a gradual accretion of many people's work."

Both Pfeiffer and Ruddle said the collaboration and information exchange between the two labs was crucial to their success.

Pfeiffer and Ruddle are two of many scientists across the world working on multiple sclerosis, a chronic autoimmune disease in which the body attacks the insulating material surrounding nerve cells. Without this insulation, called myelin, information cannot travel as fast, resulting in ascending paralysis and impaired physical mobility.

Because the disease is chronic, Ruddle said such symptoms usually develop later in life, at which point little can be done to prevent future degeneration. Thus, researchers must identify the causes of multiple sclerosis and treat the disease in its early stages to prevent it from seriously damaging the body.

"MS is the most common neurological crippler of young adults in our society," said Stephen Waxman, chair of Yale's Neurology Department. "We need to learn more about it so we can cure it. Nancy and Pfeiffer have taken an important step forward."

Pfeiffer, who has been studying multiple sclerosis since 1970, and his team observed the biology of myelin-producing cells and the changes antibodies associated with multiple sclerosis induce in these cells. They then injected two types of antibodies -- those known to contribute to multiple sclerosis and those known not to contribute -- to better understand the workings of the disease.

This process, which began a few years ago, did not always procure sufficient results, Pfeiffer said.

"[In research like this] your heart can be broken for months," he said, "and then suddenly you see something that works. Then in a flash [your work] becomes the most exciting thing in the world."

For Pfeiffer's lab, the excitement came with discovery that the antibodies reacted with a specific molecule, known as MOG, on the surface of myelin cells, he said. After this discovery Ruddle's lab took a more clinical approach, using mice models to learn more about how antibodies cause multiple sclerosis.

Ruddle's team studied the animal version of multiple sclerosis, known as EAE -- both diseases target myelin and affect extremities. While the human disease is chronic, mice experience an acute form that lasts less than two weeks.

Ruddle injected the animals with components of both human and rat MOG. They discovered the antibodies that cause multiple sclerosis recognize MOG on the cell surface and can change the MOG-making cells, while benign antibodies only recognize MOG inside the cell and cannot alter the MOG-making cell, Ruddle said.

Ruddle and Pfeiffer said their findings show promise but are not a clinical end in themselves. Pfeiffer said there is no definite timeline or course for the development of a multiple sclerosis cure, but further teamwork and collaborations will be needed to beat the disease.