by Ann Romney
If I had to get this disease, at least my timing turned out to be fortuitous. The year I was diagnosed, the theme of the annual American Academy of Neurology, then meeting in Boston, was “Revolution in Neurology”—and it did mark the beginning of a revolution in research and treatment. A few years before I was diagnosed, the first real drugs for treating the disease had recently become available, although they were still in the very early stages and no one seemed too excited about them. As Dr. Weiner told me, if I hadn’t responded to steroids, we would have tried those drugs. But by 2000 about one hundred clinical trials for new medicines were planned, in progress, or recently completed.
Incredible progress had been made since the time I was diagnosed. Without question more advances were made in diagnosing and treating MS in the last decade or so than in the previous history combined—although, in some cases at least, the disease still remains very difficult to diagnose. I have heard of diagnosed cases in which after several years the diagnosis of MS turned out to be in error, and in fact it was some other neurologic disease. When I was diagnosed, so little was really known about the disease that the old expression “Diagnose and adios” covered the “range” of available treatments. Treatment often meant doing the best to manage symptoms such as urinary complications and joint pain. That has changed completely. Investigators have picked up the scent and been relentless in pursuing the clues, successfully changing the treatment landscape, and even making the hope of a vaccine or a cure realistic.
I’ve asked Howard Weiner what my expectations should be. Will I pick up my phone one day and hear him tell me, “We got it! We got it figured out!” Probably not, he cautioned me. Most likely there will be a long series of small incremental steps, in figuring out not just MS and Alzheimer’s, but all neurologic diseases. Among those things that I personally believe we’re going to see, and maybe even soon, is nerve restoration, the stimulation of existing limbs, and amazing advances in the use of artificial limbs. I think we’ll also be able to reduce the number and severity of incidents, but as for curing any of these diseases, from everything I’ve learned, that’s still a long way in the future.
While the most important and tantalizing question—what causes MS?—has not yet been answered, much has been learned about it. It’s generally accepted by researchers that MS is an autoimmune disease in which for some unknown reason the body’s own immune system warriors, the white blood cells, attack the brain and spinal cord, specifically the myelin sheath protecting the neurons. One of the best theories about why this happens is that the immune system initially responds to a virus that in some important ways resembles the cells in the myelin sheath, and then mistakenly continues to attack healthy cells. Mitt and I have often wondered, for example, if the very bad flu I had several weeks before the onset of my disease had anything to do with it. Is it possible that it caused my immune system to go out of whack and turn on my body? We’ll never know the answer to that question.
Unlike with some viruses, though, there is no evidence that MS can be transmitted from one person to another. Recently, scientists have begun focusing on the gut as playing some type of important role in causing a range of immune diseases. The gut is the body’s largest immune system, command and control for the immune system. An estimated seven hundred trillion bacteria call it home—although no one has made a definitive count. There is some speculation that diet may even play a role. In Japan, for instance, where MS once was relatively rare, the number of new cases has coincided with significant changes in the diets of the Japanese people. Also, there seems to be some evidence that vitamin D may play a role, as the number of diagnosed cases seems to rise as the amount of available sunlight, the source of vitamin D, decreases. The farther people live from the equator, the more likely they are to be afflicted with the disease. No one yet knows why someone like me suddenly and without warning, and seemingly without any triggering event, would have been diagnosed with MS.
At least some of the most perplexing questions have been answered. Among the most puzzling mysteries that has been solved is why some people responded to some therapies while others did not. Why did I have such a dramatic response to treatment and was able to continue leading a happy and relatively healthy life while other people who got the same or similar treatment ended up in a wheelchair? Dr. Weiner published a paper in the 1980s reporting that he had successfully used chemotherapy to stop the progression of the disease. It created a stir in the medical community, because until then there had been very little progress made in fighting MS. But a decade later, when Canadian researchers tried to repeat his results and failed miserably, his discovery suddenly became quite controversial and his reputation was damaged. For Dr. Weiner, it was especially frustrating. He knew he’d found something that had dramatically helped some patients but apparently didn’t have the same impact on others. “I knew we were right,” he said. “But I couldn’t figure out why. We couldn’t find the right key to turn.” That’s probably why the doctor I saw initially followed the conservative and widely accepted protocol: go home and only after your disease progresses can we do anything to help.
One of the very basic tenets of research, going all the way back to the beginning of science, is that an experimental result is not considered valid until it has been repeated by someone else following the same recipe. The history of science is replete with people who gained attention by claiming to have made some amazing discovery, only to be exposed as frauds when those results couldn’t be repeated by researchers working independently.
Dr. Weiner eventually concluded that chemo worked mostly when it was given very early in the progression of the disease. In response to questions about his results, he had a list of patients, eventually including me, who were early in their disease whose lives had changed and maybe been saved by aggressive treatment. But the question remained: Why? What allowed some people to lead almost normal lives while others ended up crippled and in wheelchairs?
What became more and more apparent during this research was that, in fact, there were two different forms of the disease, relapsing and remitting, and progressive. Relapsing MS means that people have attacks and recover. Progressive MS, as it sounds, continues to get worse, symptoms accumulate over long periods of time without ever getting better, and there are few effective treatments. Before the therapies now used to fight relapsing MS, about three quarters of patients would eventually develop a progressive form of the disease. Most of the research being done, and all the successful research, has been centered on relapsing MS. Suddenly Dr. Weiner had at least a partial answer to the question of why certain patients responded to his treatments while others did not. There were two markedly different forms of MS. It had become clear that chemo and steroids were effective only in the relapsing stages of the disease and probably not at all effective in fighting the progressive form once it had taken root. (Clearly the Canadian researchers who refuted Dr. Weiner’s results had been treating patients with the progressive form of the disease.) Where I was so fortunate is that Dr. Weiner was able to treat me in the early stages of my disease, when steroids still would have had an effect. But as I have said, like all MS patients, I live with the knowledge that my reprieve is only temporary, that at some unknown time, for some unknown cause, it may strike again and this time harder.
The discovery of the two forms of MS led to one of the main unresolved questions about the disease: what causes the manageable relapsing disease to be transformed into the far more aggressive and debilitating progressive disease? For some reason, in some patients, the disease suddenly shifts gear into high-performance mode and races forward.
The problem with most animal models being used when Dr. Weiner did his initial study was that they would have an attack and then recover, which was the pattern of the relapsing form of the disease. But while people with progressive MS do recover from attacks, their symptoms continue to get worse, and for many years there was no animal model that mimicked this. Eventually, though, by adapting laborator
y mice bred for diabetes studies, scientists in Dr. Weiner’s MS unit were finally able to develop an animal model that successfully followed the pattern of the progressive form of the disease, which has allowed some cutting-edge research to be done. For the first time a real experimental platform existed.
Another essential advance at the beginning of the new century was made in magnetic resonance imaging. For the first time, MRIs permitted researchers to look inside the brain and see exactly what it was they were fighting—and more important, how it responded to specific treatments. It meant that they no longer were flying blind. When they tested a new drug, for example, they actually could “see” the response. In fact, the FDA has not approved a single drug to fight MS that did not ultimately show a positive effect in an MRI. Maybe equally significant, MRIs have allowed researchers to track the progression of the disease. When I go in for my annual checkup, for example, I always have an MRI to make certain there have been no substantive changes in my disease.
The advances in imaging, in being able to see the enemy, represent a significant step forward. Dr. Weiner’s partner at the center, Dennis Selkoe, spent his career studying Alzheimer’s disease and has dissected numerous brains. He’s spent years peering into microscopes and became respected as the leading Alzheimer’s researcher in the world. But it wasn’t until 2002, until these new imaging techniques became available, that he was able finally to “look” into a living brain and watch what was happening over time.
This ability to watch the progression of a disease in the human brain and spinal cord was a key factor in the establishment of the MS unit’s CLIMB study, which stands for Comprehensive Longitudinal Investigations of Multiple Sclerosis. Begun in 2000 at Brigham and Women’s Hospital, this observational, fact-gathering study looks at more than two thousand MS patients, including me, whom it has been following for a ten- to twenty-year period. It is the most comprehensive study of this kind ever done on MS.
Unlike other diseases, such as cancer, MS does not have a community that treats patients according to common protocols of therapy. That’s why even today different doctors treat patients differently. One purpose of the CLIMB study is to find those common factors in the development, treatment, and outcome for the entire universe of MS patients. Each participant in the study is following his or her own physician’s directives. Every six months, sometimes once a year, the center collects information about their neurologic status, their MRI status, and several biological samples, including blood and genetics samples. It also tracks the progress of the disease from its onset, including relapse rates, treatments, disability scores, and quality-of-life issues.
This was the first time a large MS database had been compiled, and the MRI exams serve as a visual baseline. Similar studies have proven tremendously beneficial in the past, as previously unknown patterns and connections can be derived from the information gathered. The famed Framingham Heart Study, which began in 1948, collected data every two years from more than five thousand men and women from the town of Framingham, Massachusetts. The goal was to use those data to try to understand which factors contributed to heart disease. The researchers wanted to track the habits of those people who later developed cardiovascular problems and those who remained heart healthy. That study continues today, with more people recruited over various periods since then, and has been one of the major contributors to our understanding of heart disease. It was the Framingham study that successfully identified high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity as major risk factors.
Howard Weiner compares his study to the polio experiment of 1954 in which four hundred thousand kids were vaccinated and a large number of kids received a placebo. Nine months later researchers saw who got polio and who didn’t, and the experiment was stopped and every child then got the vaccination. But this wasn’t going to be nine months. As he says of MS, “This disease progresses very slowly, so it isn’t how a patient is in two years; it’s what happens over ten years or even twenty years.”
The CLIMB study has the same ambitious goals as the Framingham study or the polio experiment—figure out what treatment has worked and what has failed and try to understand the factors that contributed to that result. I’m absolutely thrilled to be part of it. Like every patient diagnosed with a complex disease, I want to do something, anything, to help other people diagnosed with it. The frustration has been that there was so little I could do. Participating in the CLIMB study has at least made me feel that something worthwhile might come out of my illness. It really was the beginning of my involvement in helping to fight this thing.
The study has already proven its worth. When a new medicine is introduced, for example, it has enabled researchers to track its value in real time. In certain cases that also has allowed scientists to understand how to use those medicines without causing side effects. And based on papers that the CLIMB study has published, some doctors have changed their methods of treatment.
The results of the CLIMB study have already been impressive. Researching this disease sometimes seems like an archeological dig—the farther down you go, the more mysteries you uncover. A subset of progressive MS has been called malignant MS, which means it progresses unusually quickly. Within five years from the onset, for example, patients may be walking with a cane and their symptoms continue to get worse. About 12 percent of the participants in the study fit into that category. Among the proven risk factors for malignant MS is smoking. It became pretty clear that this patient population benefitted from early and aggressive treatment.
One of the initial conclusions, which was already pretty well known, was that as hard as MS is to diagnose accurately and treat, physicians were using a number of different clinical and MRI biomarkers to monitor the effect of various treatments. The numbers showed that patients who had a higher number of brain lesions when initially diagnosed, logically were more likely to fail to respond to treatment and had to be watched more closely and treated more aggressively.
What came somewhat as a surprise is that MS is often present in the body for many years before it can no longer be ignored. About 3 percent of adult MS patients experienced their first symptoms of MS during their childhood or adolescence, but were not diagnosed with the disease. The increased awareness among physicians that isolated symptoms could be signs of a serious disease conceivably would lead to an earlier diagnosis, which would mean beginning treatment sooner—which obviously could have major benefits for the rest of a patient’s life. CLIMB study statistics also indicate that those children who are diagnosed with MS generally experience two to three times as many relapses as adults. By the end of 2014, more than fifty papers had been published based on data collected in the CLIMB study. Equally important, Google is in discussion with the MS Center to use its medical computational abilities to drill down into the statistics to try to find additional correlations.
One of the major initiatives currently being pursued as part of the CLIMB study is to develop so-called biomarkers, which are used to monitor the progress of the disease and are crucial for conducting studies. An MRI is the most widely used biomarker; it replaced an analysis of spinal fluid, which was obtained through sometimes painful spinal taps. There is considerable emphasis on developing a blood test for MS that will allow physicians to determine quickly, painlessly, and inexpensively whether the disease is active in a patient, whether it is the relapsing or progressive form, and if and how the patient is responding to various medications. Throughout the history of the CLIMB study, the center has collected and has available more than seventy-five thousand blood samples from more than three thousand patients at all stages of the disease. A recent breakthrough was the discovery of micro-RNA circulating in the bloodstream that can be used to diagnose the disease and determine its stage.
Like so many other chronic diseases, in addition to taking a physical toll, MS also can cause serious psychological damage. In fact, this disease affects every aspect of your life—and often, b
ecause many MS patients look perfectly healthy and may be able to lead close-to-normal lives, other people just don’t get it. Believe me, I’ve seen people question MS patients who dared park in a handicapped spot; I’ve heard people say about me, “Well, she doesn’t look sick.” I know that some people actually believe my disease had some political benefit. I understand people think the exhaustion can be resolved simply by our getting more sleep. Many MS patients have experienced that same reaction: “You don’t look sick. Why can’t you just … just do anything.” If people could only see what was going on inside.
On those nights I was just too tired to go to a scheduled event or those days when I had to stop campaigning, I really felt I was letting people down. When that happens it is incredibly frustrating. Fortunately, another aspect of the CLIMB study is attempting to assess the social damage inflicted by MS. Obviously the disease can make it difficult for people to keep and hold a job. The rate of unemployment for MS patients has been as high as 80 percent. That’s a huge number. Those people who are working also may experience greatly increased absenteeism as well as what is called presenteeism, meaning reduced productivity while at work. About half the working people in the study reported that their productivity had been affected, which also meant that the possibility of advancing in their field or getting that raise was limited. As researchers reported, MS patients felt constrained in the amount or kind of work they did, they accomplished a lot less than they intended, and they were not as careful. And depression, greater fatigue, anxiety, and decreased quality of life could all be associated with that reduced productivity.