By Sally Squires
Washington Post Staff Writer
Tuesday, May 4, 1999; Page Z13
For years, family, friends and physicians who care for people with multiple sclerosis have worried about how to slow the progression of the chronic neurological illness. MS strikes in young adulthood, slowly robbing patients of their motor skills and sometimes causing blindness. Now a new generation of MS drugs containing the human protein beta interferon is providing the first hope that the disease may be controlled, if not conquered. The promise in interferon drugs is helping to change the public perception of a disease that affects 250,000 Americans. The latest evidence suggests that one of these interferon drugs--Avonex--can even slow the shrinkage of brain tissue that occurs in some patients.
No cure exists for MS, but since 1993, three drugs containing interferon have been approved by the Food and Drug Administration to treat the relapsing-remitting form of the disease. A team of researchers from the Cleveland Clinic reanalyzed clinical data submitted to the FDA on Avonex and found the first evidence that it can protect patients against the gradual loss of brain tissue. They presented their findings last month in Toronto at a meeting of the American Academy of Neurology.
An estimated 200 new cases of MS are detected each week in the United States, according to National Institute of Neurological Disease and Stroke (NINDS). Women are twice as likely as men to get MS, and whites are twice as likely as people of other races to develop the disease. The illness costs an estimated $2.5 billion annually in direct medical costs, lost work and disability expenses, according to NINDS.
What causes MS to occur is not known, although researchers have suspected that it may be a combination of environmental factors and genetic susceptibility. One theory is that perhaps a viral infection triggers the disease in vulnerable people.
However it begins, MS causes the body's immune system to attack nerve tissue in the brain, forming patches called plaques. As the disease progresses, the myelin sheaths that surround nerves can also be affected and gradually destroyed. Myelin is a fatty covering that insulates nerves and enables high-speed messages to move between the brain and other areas of the body. As the myelin is slowly destroyed, the MS symptoms grow worse. Motor skills are frequently affected, making walking difficult. The disease can also attack the optical nerve, resulting in vision loss and blindness.
MS is usually diagnosed between the ages of 20 and 40 years, but because symptoms can wax and wane, the disease may go undetected until later in life. The fluctuating symptoms also make assessment of treatments difficult: Researchers must be careful that therapy is the reason for improvement and not the natural cyclical course of the disease. Most patients begin with relapsing-remitting disease, a cycle marked by flare-ups then periods of remission. Many of these patients eventually develop primary progressive MS, which is characterized by gradual decline and no distinct remissions. About 20 percent of MS patients have a mild form of the disease, which shows little or no progression after the first attack.
The researchers from the Cleveland Clinic Foundation showed that the regular use of Avonex seems to help significantly reduce the brain shrinkage caused by MS.
In the two-year study, 70 patients with relapsing-remitting MS were given weekly intramuscular injections of Avonex and compared with 70 similar patients who took injections with a placebo. Both groups were in turn compared with 16 healthy individuals.
During the study's first year, there was no difference in the amount of brain atrophy between the two groups of MS patients. But during the second year, the researchers found that Avonex reduced the amount of brain shrinkage in MS patients by 55 percent compared with people receiving the placebo.
"We've known for quite some time that there is a loss of brain volume as a consequence of MS," said Stephen Reinhold, vice president of research programs at the National Multiple Sclerosis Society, which helped fund the study. "It's unclear whether this loss is of nerve fibers or supportive brain tissue. This is a dramatic demonstration of this phenomenon."
How such a loss relates to more acute symptoms is not clear. The findings do, however, underscore the importance of early, aggressive drug treatment for MS, even when symptoms don't seem very significant, researchers said.
Richard Rudick, a coauthor of the study and professor of neurology at the Cleveland Clinic Foundation's Mellen Center for MS Treatment and Research, said that MS patients in remission are often reluctant to take weekly injections of expensive medications. The drugs cost about $10,000 a year and can have unpleasant side effects.
The findings suggest that a destructive brain process "is ongoing in patients who are clinically stable," Rudick said. "Now we know that at least one of the available drugs is able to stop this. . . . It suggests that patients be treated pro-actively at early stages of the disease." How the other two inteferon drugs--Betaseron and Copaxone--will stack up against Avonex in preventing brain shrinkage in MS patients is not known, because they haven't been studied yet for that purpose. "This is the first report of any drug in the MS field [being effective] on the loss of brain tissue," Rudick said, noting that additional research could find other ways of preventing the loss.
While the findings are significant, "they do not mean that Avonex is the drug that everyone with MS should be on right now," Reinhold said. "It's a real, personal choice that the individual and his or her physician need to make together."
The Cleveland Clinic team has also developed better ways of monitoring the brains of MS patients with a modification of magnetic resonance imaging. Rudick and his colleagues altered the standard MRI to enable more detailed measurement of the brain to better assess the impact of different MS drugs. The altered MRI test takes about 10 minutes and costs about $200 to perform, compared with $1,000 for the full, hour-long MRI. "This gives us a potential way to make precise, accurate measurements [of brain changes] that could be used to determine how MS drugs stack up against each other," Rudick said.
MRI is routinely used to measure brain lesions that can occur with multiple sclerosis. But the number of brain lesions often does not correspond well to symptoms. The modified MRI technique measures not only lesions but the shinkage of tissue in the brain, a more accurate assessment of how the disease is progressing or is staying in remission.
"These are exciting findings," said A.P. Kerza-Kwiatecki, who heads the MS program at the National Institute of Neurological Diseases and Stroke, which helped fund the Cleveland Clinic's research. "There is no reliable marker to assess the disease status or progression or remission in MS. . . . If this is a true marker of MS, then we have got something here."
Such a tool could prove to be particularly valuable for scientific study. "It will help us get more information about the progression of the disease, the impact of the pathology in the brain and it can help us understand treatment effects," Reinhold said. Just how such a tool will be used to monitor individual patients has not been determined.
In other news at the neurology academy's meeting, researchers from the pharmaceutical company Immunex reported that a drug used to treat pain in patients with advanced prostate cancer may also be useful against MS.
Results of a three-year clinical trial of the drug, Novantrone, showed that it helped reduce flare-ups and delayed disability in patients with hard-to-treat progressive MS. About 120,000 people with MS have the progressive form of the disease. No approved treatments are available for this form of the disease.
Half of the 194 people in the study received intravenous administration
of Novantrone once every three months for two years. The other half received
a placebo. Nearly half of those receiving the placebo experienced significant
disability compared with 17 percent of patients who received the highest
dosage of Novantrone and 24 percent of participants who received a lower
dosage, the study found. During the year following the three-year trial,
doctors continued to observe patients and found that relapses remained
lower in the patients who had taken the drug compared with those who had
received the placebo. The mechanism of Novantrone on MS is still unclear.
But scientists believe that it suppresses action of the white blood cells
that attack the myelin sheath.