Vanderbilt researcher may have unlocked clues to cause of MS
By Matt Pulle
FEBRUARY 14, 2000: Not long ago, you could be suffering from all the textbook symptoms of multiple sclerosis--the steady loss of coordination, sight, or even the simple ability to walk or just dial a phone--and have a doctor tell you that this very real dimming of your basic functions was "all in your head." Because the physiological clues of the disease are hard to detect and because it affects nearly twice as many women as men, physicians often failed to take many of their patients seriously and sometimes referred them to a psychologist. In her book All of a Piece, multiple sclerosis patient Barbara Webster recalls how her family doctor told her that the reason she struggled to walk more than a block at a time was because she was involved in a "bad relationship."
In the last 15 years, however, scientists have revolutionized how doctors detect and treat MS. In the late '80s, MRIs, which use magnetic force to capture a microscopic image, made it easier to identify the scarred nerve cells that form the devastating footprints of MS. Shortly after, a new generation of potent, high-tech drugs called interferons were introduced. They help regulate the function of the immune system. Compared to the other treatments for the disease, including steroids, the new drugs had fewer long-term side effects and were more likely to halt the creeping of the plaques and lesions throughout the central nervous system.
Despite all this progress, the outlook remains bleak for most people diagnosed with MS. There's no known cure and even the new drugs work only some of the time, and then only with limited results. Still, the medical war against multiple sclerosis wages on, and perhaps the most exciting front--research that in time might yield a disease-killing vaccine--is taking place right here in Nashville.
Depending on their point of view, his colleagues regard him as either a pioneer or an iconoclast. His patients, however, think of him as a savior.
Dr. Subramaniam Sriram, the mild-mannered, if exacting, director of Vanderbilt's Multiple Sclerosis Center, may be the only doctor in the world who is experimenting with giving his patients antibiotics to attack not just the symptoms of the disease, but the root cause. Practically alone among his peers, Sriram believes that MS is just another infectious disease and suggests that a relatively benign course of antibiotics could be used to treat it.
The early results of the research being conducted by Sriram, who is being joined by colleagues Chuck Stratton and Bill Mitchell, are inconclusive. But they look very promising. Patients who for years have helplessly watched their basic motor functions deteriorate now seem stable. Others have radically improved. One of Sriram's patients, a young Tullahoma man, was confined to a wheelchair and couldn't dial a phone. Now, he can walk, go hunting, and drive a car.
As news of his research has spread, Sriram has received national attention and hopeful calls from MS patients around the world. Some in the medical community, however, have greeted his work with intense suspicion. Some scientists are necessarily wary about drawing conclusions from a few success stories. After all, if Sriram's hypothesis is proven true, it could shatter bedrock assumptions about what kind of disease multiple sclerosis is.
"His research is very promising, but there is a lot of skepticism out there," says Amy Brown, program coordinator for the Middle Tennessee chapter of the Multiple Sclerosis Society. She says some scientists might hope Sriram is wrong, so they can be the ones to find a cure instead.
With a modest smile, Sriram doesn't explicitly assign ulterior motives to his many doubting peers. But he's unusually frank about where they stand.
"I think they all wish me well," Sriram says. "But in their heart of hearts they think I'm wrong."
Among the most prevalent diseases of the central nervous system, MS affects nearly 2.5 million people around the world, including 2,000 here in Middle Tennessee. In a patient with the disease, the fatty material--known as myelin--that covers and insulates nerve cells becomes inflamed, and scars or plaques form. (Multiple sclerosis means, simply, many scars.)
It's that inflammation of the myelin that ultimately causes the symptoms of MS. Nerve fibers help communicate impulses to and from the brain. When MS damages the protective covering of those fibers, basic and routine functions are disrupted. The effects of a weakened central nervous system can vary--one person with MS might struggle only when jumping rope while another can't turn off a night-light.
Although multiple sclerosis was identified more than 100 years ago, nobody knows what causes it. Researchers have long suspected that MS is an autoimmune disease, along the same lines as lupus and rheumatoid arthritis. An enduring medical mystery, autoimmune disorders feature an out-of-control immune system fighting healthy cells rather than protecting them. The cause of suspected autoimmune disorders remains unknown, although with MS, most scientists believe that a pathogen or some kind of genetic deviance prompts the immune system to betray the body. (There is strong evidence that MS has a genetic component. Some ethnic groups are more prone to acquiring the disease than others. People with a northern European ancestry, for example, are more prone to having MS, while Asians are far less likely.)
Indeed, so many physicians assume that MS is an autoimmune disease that in some circles, it's taken as fact. Defying nearly every other scientist in his field, Sriram instead thinks that MS is an infectious disease, caused by the everyday bacteria, Chlamydia pneumoniae. According to Sriram's laboratory findings, that bacteria lurks in the spinal fluid of disproportionately high numbers of MS patients--and might well be the culprit behind the disease.
In a story appearing in Mirabella magazine, renowned science writer Hillary Johnson notes that the implications of Sriram's hypothesis are staggering.
"That MS may be caused not by an inscrutable immunologic or genetic abnormality but by a germ--the kind of banal organism that sparks such illnesses as strep throat and urinary tract infections--could dramatically transform the way doctors think about and treat the disease."
Basically, if Sriram's hypothesis proves true, scientists could develop a vaccine for MS and relegate it along with polio and smallpox to the dustbin of medical history. That might take a while. For now, Sriram is already putting his hypothesis to the test by giving his patients the same course of treatment doctors have used to treat infectious diseases for generations. He does this as a last resort, typically after other more conventional forms of treatment have failed.
Brad Lamons used to work as a deputy sheriff for Bedford County, where a day in his life could include everything from serving warrants to settling drunken bar fights. A former offensive lineman for the Tullahoma High School football team, Lamons, with his robust frame and assuring personality, had long exuded Southern grit and All-American vitality. He hunted, played sports, lifted weights, and cheered for his beloved Tennessee Vols.
In January 1996, Lamons barely broke a sweat in passing the Army National Guard's fitness test. He managed 42 push-ups and 52 sit-ups, both in less than two minutes, and ran two miles in around 16 minutes.
Shortly after the fitness test, Lamons began to notice a sharp pain in his back and thought he pulled a muscle. The pain, however, grew progressively worse and soon the left side of his body was completely paralyzed. A local doctor gave him a round of steroids, and Lamons soon began to feel better.
One month later, in what he thought would be a routine follow-up visit to the doctor, Lamons was diagnosed with multiple sclerosis. Feeling as strong as he did just a few months earlier, Lamons wasn't worried.
"I didn't even know what MS was," says Lamons. "And since I was in remission, I figured I could deal with it."
That same month, Lamons got married. It was a busy time in his life. Soon, however, it would all unravel.
For some patients, multiple sclerosis can be like a rag-tag guerrilla army, lurking under cover, always unpredictable, and ready to attack and retreat, seemingly at whim. In the spring of 1996, Brad Lamons' multiple sclerosis was on the attack. Not long after his wedding, Lamons endured terrifying bouts of dizziness, heavy fatigue, double vision, and bladder control problems. The medication he was taking was not working. At the start of the summer, a scant six months after he excelled at the National Guard's rigorous fitness test, Lamons couldn't even walk.
"I was scared, my eyesight was going out, I had no control of my bladder or bowels," he recalls. "I was totally paralyzed. I could not even pick up the phone. My speech was slurred."
After a referral from a doctor at Baptist Hospital, Lamons visited Dr. Sriram in early July of that year. When examining patients, doctors sometimes rate their health on a scale of one to 10. With one being normal and 10 being--for all practical purposes--dead, Lamons was rated an eight.
Conventional therapies for MS had failed with Lamons, and Sriram didn't want to subject him to even stronger drugs. But after a discussion with colleagues Chuck Stratton and Bill Mitchell, Sriram decided to test for the presence of the bacteria Chlamydia pneumoniae in Lamons' spinal fluid. When the test came up positive for the bacteria, Sriram took Lamons off his main drugs and placed him on a course of long-term antibiotics. According to Sriram, no other doctor would have chosen that treatment.
"The thinking is not that MS is an infectious disease caused by bacteria," he says.
But in stark contrast to what other physicians might have predicted, Lamons' condition began to rapidly improve. By the end of July, with the aid of a walker, Lamons was ambulatory. By the end of August, he was using a cane intermittently, and the coordination in his upper body was improving. By January 1997, Lamons could walk on his own. Within a year, with the disease on the retreat, he stopped taking the antibiotics.
Today, Lamons no longer chases down drunks for a living and would not be able to pass the National Guard's fitness test. He has suffered permanent nerve damage and still endures headaches and other flu-like symptoms. Multiple sclerosis has taken its toll. His marriage crumbled. He had to leave his job and was forced to move back home with his parents.
But with the loving help of his family, along with his ex-wife--they remain great friends--Lamons is living a full and promising life. He's taking classes in computer technology and hopes to land a job in that field. And while he once wondered if he'd watch the world from a wheelchair, Lamons, now 27, can walk on his own, drive a car, and grip and fire his hunting rifle.
The symptoms of MS can ebb and flow, and Lamons knows that, while he's contained the disease for three years, it could still resurface with a vengeance. But if the antibiotic treatment did in fact kill the bacteria that caused this disease, then Lamons and Sriram might have won a battle with MS and marked a turning point in the hundred-year war against the disease.
"We're in uncharted territory. We don't know what's going to happen six months or a year from now," Lamons says. "But I'm thankful I can walk and see. I can feed myself. There are so many people who can't do anything."
But not long after she moved from Ann Arbor, Mich., to Nashville in 1992, her condition deteriorated badly, and she gradually lost the full use of her legs, arms, and hands.
During this time Min had been seeing Dr. Sriram, who then subscribed to the conventional wisdom that MS was an autoimmune disease.
As a result, he put her on chemotherapy to help suppress the disease and steroids to reduce inflammation. But not only was that treatment failing, it prompted strong side effects. Min began losing her hair, while the steroids caused her to have wild mood swings.
Around this time, Sriram began to doubt not just the traditional view of the disease, but also the traditional means to treat it.
"The central tenet of all these hypotheses is that if you suppress the immune system sufficiently, you can reverse the disease. But I didn't see that happening," Sriram says. "We have done all kinds of things to MS patients to suppress the immune system with only marginal results."
Once Sriram started suspecting a bacteria might be the culprit, he began prescribing antibiotics to a select group of patients. Margaret Min was one of them. Nearly three years later, Min remembers what he told her.
"He very clearly said that his goal was to save my left hand," she says.
That might seem like a modest pronouncement. But for nearly six years, multiple sclerosis had been steadily confiscating Min's basic functions. Now the disease, perhaps because of the antibiotics, has been stopped in its tracks. And Min now has use of her left hand--a noteworthy event considering how hard it is to turn back this disease.
"Two years ago I could barely use a hand. I would struggle to dial one number on a phone. Now I can feed myself, pick up a handset and write, or operate my wheelchair," says Min. "I've had progressive MS for so long. This is the first time I've actually regained a function. Dr. Sriram is reluctant to say he did it, but I don't see how it could be anything else."
Unlike conventional wisdom in, say, politics, which can be advanced or debased after a couple of events, a scientific hypothesis can take years to evaluate. So far, other laboratories have had mixed results in verifying Sriram and his team's vital premise that Chlamydia bacteria exists in the spinal fluids of a high percentage of patients--thereby triggering MS.
Dr. Patricia O'Looney is the director of biomedical research for the New York-based National Multiple Sclerosis Society. Like most doctors, she is cautious in evaluating Sriram's findings and resulting hypothesis.
"Certainly it's provocative and it's unique in thinking of different possibilities in what may possibly be a role in triggering the disease. But it's certainly not a fait accompli. Other laboratories will have to substantiate his research, and there is some controversy. In some reports from other laboratories, these findings have not been reported."
But if Sriram doesn't yet have the weight of scientific research on his side, his antibiotic treatment is piling up very real and impressive results. Out of the 13 patients who have completed nine months to a year of antibiotic treatment, 11 have either improved or stabilized, while only two have gotten worse.
Dr. Martin Wagner, a local neurologist, says that while Sriram's treatment might hold promise, it's still too early to make a definitive case for it.
"We don't know if the antibiotic treatment improved these patients or they improved on their own," he says. "The nature of MS is that many patients may have a relapsing and remitting course."
A natural skeptic himself, Sriram concedes that his treatment is "way out of the mainstream." But if he's proven right, not only will antibiotics be used to roll back the steady encroachment of MS, but researchers might then be able to develop a vaccine that could remove it from the formidable lineup of debilitating diseases.
In the here and now, though, Sriram continues to surprise not just his peers but even his patients with his unorthodox treatment. When he first recommended antibiotics to Kristin Searfoss, she concedes she was a little suspicious. "So many times I would take a new medication and continue to get worse," she says. "But when I saw him, I told him I was ready to try anything."
For nearly seven years, Searfoss had been experiencing symptoms of MS. It began on a hot August day in 1991, when she kept tripping on a hike through a Canadian forest. Shortly after she returned to her home in Louisville, Ky., she struggled to walk around the local reservoir. Throughout that fall, Searfoss' knee bothered her, and routine acts, like taking out a contact lens, suddenly became difficult.
Over the next year, she saw two different doctors, both of whom said nothing was wrong with her. Neither one, however, thought to watch her walk. If they did, she says, they might have noticed something was definitely wrong.
Within a year, Searfoss, who had been active her whole life, couldn't jog. She was feeling clumsy and tired all the time. Five years later, she was in a wheelchair, unable to walk except for short distances. Soon she lost her job as a writer, and in December 1997, she moved to Nashville. One month later, she visited Dr. Sriram.
For a while, Searfoss' condition continued to worsen, and by November 1998, Sriram prescribed antibiotics. It had been more than seven years since her hike in Canada, and ever since Searfoss had watched her motor abilities slowly, but irrevocably it seemed, fade away.
Yet within six months, Searfoss started to improve. Her parents noticed when they came to visit her. In her medical diary, she noted that her hands were stronger and more nimble. She could now use scissors, nail files, tweezers, toothbrushes, and pens.
Today, Searfoss has no new symptoms of MS. And while she remains in a wheelchair, she has retained use of her upper body, an ability she thought she was almost sure to lose. Now 33, Searfoss, a freelance writer and a talented painter, hopes to get married and even have children.
"I know for me this treatment has worked," she says. "I know the scientific process is so complicated, but I think he discovered one piece of the puzzle, and for me, it's made all the difference in the world."
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