Although Still No Cure, New Treatments Developing for MS by Carolyn Cosmos Multiple sclerosis (MS) is an erratic and unpredictable disease. Chronic but not typically fatal, it launches an ongoing assault on the nervous system that damages the spine and brain. Symptoms come and go for reasons unknown, and the course of the disease and these symptoms vary widely, but problems can include numbness and fatigue, minor movement difficulties or paralysis, cognitive decline and blindness. Multiple sclerosis affects 2.5 million individuals worldwide, three-fourths of them women. About 6,000 people in the Washington, D.C., metropolitan area have the disease. My friendóI will call her Marthaóis one of them. Now 78, she was diagnosed with MS in her mid-40s and until recently, led an active life while her MS ebbed and flowed, sometimes disappearing, other times forcing her to use first her walker and then her motorized scooter. Over the last two years, Marthaís symptoms have gotten worse. As happens about half the time with ìrelapsing-remittingî MS, Martha developed a progressive version of the disease. She uses a wheelchair and relies on her husband for daily tasks. However, although her memory sometimes fails her, her wicked wit does not. Good Cells Gone Bad What causes MS? Nobody knows for sure, but it appears likely that genetic factors interact with outside triggersóasbestos or a virus, for instanceóto set it off. Studies suggest that a large number of genes, 30 or 40, may be involved, along with a strange array of triggers such as a lack of sunlight. MS is an autoimmune disease, part of an unholy family of disorders in which the body turns on itself. Included in this family are lupus, diabetes, rheumatoid arthritis and, possibly, heart disease. How does MS do its dirty work? It hijacks your molecules. Almost every cell in your body has a marker on it that identifies it, and your immune system can ordinarily detect the difference between these cells and foreign invaders such as a virus or cancer tumor. When dangerous stranger cells appear, the immune system attacks them. The immune systemís weapons include macrophage cells that eat strangers and digest them and natural killer cells that deliver toxic chemical blasts at foreign contact. More sophisticated are the antibodies, ìsmart bombî molecules that lock onto specific disease targets. Redness around a wound or a high fever tells you that an inner body battle is going on. In multiple sclerosis, the immune cells that ordinarily protect you from harm turn against you. They attack the nerves in your brain and spinal cord as if they were foreign, damaging myelin, a protective sheath around the nerves, and the nerves themselvesóthus interfering with central nervous system communication. New Treatments for MS When it comes to medical solutions, the MS mantra has been, ìThere is no cure.î However, in a striking tribute to scientific research, new treatments that can slow and sometimes reverse the disease have been pouring in over the last 10 years, and there are more of them in the pipeline. Promising basic research is regularly surfacing, with significant advances made in the last year. In fact, MS experts are now more apt to say, ìThere is no cureóyet.î Currently, MS patients have turn to several drugs that affect the immune system in positive ways, including beta interferons, as well as Copaxone and Novantrone, which is also a cancer chemotherapy treatment. At the end of 2004, a brand new immune-system treatment, Tysabri (natalizumab), was approved for treating relapsing forms of multiple sclerosis by the Food and Drug Administration. ìOn the therapy front this was a significant step forward,î said Dr. Timothy Coetzee, director of research training programs at the National Multiple Sclerosis Society based in New York City. ìIt was the big MS news for 2004.î Tysabri is an antibody treatment. ìIt locks onto [harmful] molecules and prevents them from getting into the brain,î Coetzee explained. A clinical trial that compared Tysabri to a placebo or inactive substance looked at 942 people with MS at 99 sites worldwide. Tysabri reduced the MS relapse rate by large amounts, up to 66 percent. Itís also valuable to MS patients, Coetzee noted, because unlike other MS drugs that have to be injected daily or weekly at home, Tysabri is infused in a clinic or doctorís office once a month. And itís likely to be covered by Medicare. That coverage is critical: Tysabri costs a stunning $23,500 a year. Betaseron is $17,827, and Copaxone is $16,026. New Look at Old Drugs Another ìnew possibility and exciting treatment approach,î Coetzee said, is based on already approved prescription drugs used to lower cholesterol and treat heart disease: statins. Since 2002, researchers discovered that drugs such as Lipitor can somehow rehabilitate those MS ìgood cells gone badî in rats and mice. Three safety-checking clinical trials are under way to see if they can do the same thing in humans. Similarly, a drug now used to treat people with Alzheimerís disease, donepezil (Aricept), has been tried out in a small number of people with MS. A clinical trial conducted at the State University of New York Stony Brook found it helped 65 percent of patients do better on memory tasks compared to 32 percent improving with a placebo. Larger studies are now needed. A third new approach to MS based on existing options deals with prevention, although it hints at treatment possibilities. Two studies indicate that getting more sunlight or taking vitamin D supplements may well reduce the risk of getting MS later in life. One found that pregnant women who took vitamin D had children who were less likely to develop MS later in life. Another study linked higher rates of MS to less exposure to sunlight. Interestingly, MS rates are higher in northern countries where people get less sunlight. There are numerous other promising research avenues that involve studies done with animals or human clinical trials (160 trials are under way around the globe), with the National Multiple Sclerosis Society helping to fund many of themóto the tune of nearly $35 million last year. These promising paths include more research involving familiar products. At the University of Illinois at Chicago, a drug commonly used to treat diabetes, pioglitazone, is being examined for its effect on the immune system and MS. At Johns Hopkins University in Baltimore, Md., research is looking at whether ordinary antibiotics such as penicillin can prevent or slow nerve damage. Other research is asking whether ginkgo biloba, frequently used in complementary and alternative medicine, can help with MS-based cognitive decline. And studies are taking a fresh look at hormones, particularly those in the thyroid and the sex hormones estrogen and testosterone. Advances based on genetic research are also flourishing. Important pediatric work with children who develop MS at an early age is looking into genetic factors likely to have a stronger influence than environmental ones when MS develops in someone so young. This could lead to gene-based treatments or even a cure. Researchers have also recently pinpointed in animal studies genetic factors involved in myelin repair, looking at what turns repair mechanisms on and off in mice. Carolyn Cosmos is a contributing writer for The Washington Diplomat.