Hope for Multiple Sclerosis

by Guy McKhann, M.D.

October 11, 2012

There are a group of diseases called “autoimmune” diseases, in which a person’s immune system goes awry and attacks the organ systems. Rheumatoid arthritis, inflammatory bowel disease, and the skin condition psoriasis fall into this category. In the peripheral nervous system the acute paralyzing disease Guillain-Barre Syndrome is an autoimmune disease, and in the central nervous system multiple sclerosis is also in this category.

Multiple sclerosis (MS) is a disease that is spread in time and place. The lesions of multiple sclerosis can occur anywhere around the brain and spinal cord (spread in place) and can occur at different times. Thus in the most common form of the disease, the relapsing and remitting form, a person can have attacks of disability that are very heterogeneous—loss of vision in an eye, sensory disturbance in a limb, weakness of the legs—all depending on where the disease has struck.

The pathological process in MS is an attack of immune cells on myelin, the material covering nerve fibers. We call that disruptive process “demyelination.” Myelin is like the insulation on a wire in your house. If the covering is disrupted, the electricity doesn’t get through. The same process happens in the nervous system. Once an attack occurs, the brain can recover and form replacement myelin; in some cases, an attack of demyelination can be self-limited. Why all this occurs is not known. There are genetic factors, and presumably something triggers the disease, but no clear-cut cause has been found.

Before the days of modern imaging, analysis of the brain of someone with MS would leave researchers amazed by the large number of demeylinative lesions that had been clinically silent—that is, the lesion was there, but there were no signs of damage to a person's abilities or behavior. Now that has all changed. With modern imaging, particularly MRI, one can see the demyelinative images, and see them come and go over time.

Treatment has been aimed at altering the underlying immune process. For many years, treatment included blasting at the immune system with high doses of steroids, like prednisone, or using immuno-suppressive drugs as are used in suppressing rejection of a transplanted organ. These attempts were only partially effective and had unwanted side-effects. A second approach, using an interferon, has been the leading approach to therapy in recent years. Interferons are proteins that suppress immune activity. In a number of studies interferon has been shown to reduce attacks by about one-third, and to be associated with many fewer lesions as seen on MRI.

Until recently, people with MS had to inject themselves with interferon every day. Besides the local reaction to the shot, patients often had flu-like symptoms, and so many did not always keep up with this medical regimen. About five years ago, oral preparations became available. The latest is a new preparation, not yet approved by the FDA. Two studies published in The New England Journal of Medicine compared this new drug, still identified by its industry name, BG-12, with a placebo or another drug. BG-12, taken by mouth twice per day, reduced the number of new lesions by 70-99 percent. Further, over a two-year period, it reduced the progression to disability by 38 percent. The major side effects were related to gastrointestinal functioning, with some patients experiencing cramps, diarrhea, and vomiting. These symptoms decreased over time and most patients were able to continue using the drug. Slightly different forms of the drug have been used, particularly in Europe, to treat psoriasis. Thus there is experience with safe, long-term use of the drug in humans.

There are still many questions. MS is a disease that often starts when a person is in his or her early 20s. Are we talking about life-long therapy? What would be the criteria for stopping a drug? Multiple sclerosis has gone from being a disease that we could diagnose and then watch helplessly while a person became disabled to a disease that we can treat early to decrease the number of attacks and perhaps alter the long-term course. We can add MS, treated with a drug like BG-12, to the list brain diseases where therapy makes a positive difference.

For those interested, there is an excellent accompanying editorial in The New England Journal of Medicine by my colleague, Allen Ropper of Harvard, commenting on the current state of treatment in MS.