When renowned pathologist Luther E. Lindner found "strange organisms" in human blood and tissue, he was intrigued. Now Lindner along with a Texas-based company called Pathobiotek say a newly discovered, blood-based bacterium may be the long-sought trigger for multiple sclerosis, chronic fatigue syndrome, and other forms of autoimmune disease.
One of the most confounding diseases of modern times, multiple sclerosis (MS) is caused by destruction of the fatty myelin sheath that normally insulates neurons and enables signals to pass from one nerve cell to the next. Symptoms, when nerve signals are subsequently slowed or halted, range from mild numbness in the limbs to dramatic cognitive decline, paralysis, and loss of sight.
|Multiple sclerosis' cause is still unknown.
Most experts believe that the destructive process is autoimmune in nature, spurred when the body's immune cells attack the cells of the central nervous system. Scientists have, in recent years, identified the rogue immune cells involved in the destruction, even pinpointing the receptor sites that cause these cells to latch onto myelin, prompting the mayhem to begin. But while researchers have mapped the process, they don't know what sets it off. Prime suspects have been viruses, already implicated in demyelination of nerves. Yet investigation of more than a dozen viruses, including measles, canine distemper, and herpes (HHV-6) have failed to show cause and effect.
Now a Texas-based company called Pathobiotek Diagnostics says a newly discovered, blood-based bacterium may be a trigger for MS, chronic fatigue syndrome (CFS), and other forms of autoimmune disease. It all started a few years back when respected pathologist Luther E. Lindner joined colleagues and investors to pursue "the strange organisms" he'd found in human blood and tissue over the years. As part of that effort, a researcher working under Lindner used a novel culture system to see if he could identify the spirochete Borrelia burgdorferi in a patient thought to have Lyme disease, often so similar to MS and CFS that the conditions may seem indistinguishable. "Lo and behold," says Lindner, "we saw a few bacteria wiggling around, but they were not spirochetes and, so, clearly not B. burgdorferi or Lyme."
|"The general dogma is that the bloodstream of normal people is sterile."
Lindner was, to put it mildly, intrigued. "The general dogma in medicine up until very recently," he explains, "is that the bloodstream in normal people is sterile. It was not supposed to have bacteria floating around in it, but there they were."
Pursuing the discovery, Lindner studied a group of 66 patients with CFS, MS, and other forms of autoimmune disease, including rheumatoid arthritis and lupus. Focusing on MS patients alone, he made a notable observation: Those with symptoms had the odd bacteria present in high numbers, while those in remission generally did not. To determine whether the bacteria and the symptoms were truly related, he began treating symptomatic patients empirically with antibiotics, changing medications when symptoms remained. If patients were treated long enough, from two to six months and in some cases more, he says, "about 50 percent improved. We observed that symptomatic treatment correlated with levels of bacteria in the blood."
|"We cannot recommend this treatment at all."
Despite his ability to improve the outcome for many patients, however, there were roadblocks to overcome. For one thing, a percentage of patients responded to antibiotic treatment by getting drastically sicker than they'd been before. It turns out, says Lindner, that antibiotics in this subgroup of patients stimulated bacterial growth, an effect he has traced to a specific pump in the bacterial cell walls. Thus, even though treatment was helpful for many patients, it was still a game of Russian roulette. "The results are not predictable. Without tests to identify antibiotic sensitivity levels in each patient," he says, "we cannot not recommend this treatment at all."
In addition, the culturing system Lindner used to guide his research was crude. "It relied basically on microscopic observation and microscopic counting," he says. "You can't be a hundred percent sure of what you're looking at under the microscope." In order to be sure of his findings, he had to look at the organism at the genetic level, sequencing its DNA. To take Lindner's work to the next level, Pathobiotek has been focusing on a technology platform aimed at characterizing and quantifying the newly found organism through state-of-the-art molecular and microbiological tools. One result has been identification of the organism's DNA by polymerase chain reaction (PCR), proving it is truly unique. Reflecting this finding, Pathobiotek has registered "Human Blood Bacterium," or HBB, as United States Patent 6,255,467, issued in July 2001.
|"We can grow them from everyone."
The company has also been hard at work on improving culturing techniques using DNA analysis for confirmation of organism identity. "It has been a long, slow process," says Lindner, "but the new culturing system is several orders of magnitude better than the original." One result of culture advancements has been the finding that the organism is present, in low number, in all or nearly all people. "We can grow them from everyone," he states. The Lindner team has also learned that the organisms consist of three or four closely related species of Methylobacteria, a class usually found living in the environment. "So far we haven't found a particular species or strain to correlate with whether or not the patient has symptoms," Lindner adds, "though we continue to look. And although we have been looking fairly hard, we have yet to find any mechanism that would explain why certain patients have symptoms while others do not. We are now working on quantitative PCR to see whether we can confirm our original, crude associations in a more precise way."
The company also hopes to help physicians and other researchers consider this new organism when diagnosing, treating, or studying the spectrum of autoimmune disease that includes CFS and MS. Toward that end, it intends to market several kits enabling researchers to confirm the presence of the microorganism from either serum or culture samples. New techniques involving quantitative PCR, as well as monoclonal and polyclonal antibodies currently under development will soon allow labs to assay the varying levels of the microorganism in humans.
|Niacin tends to turn up the pumps.
The company is also trying to understand the mechanism of the cell-wall pump that can respond to antibiotics by making some patients especially ill. "We don't know what the pumps are moving in and out of the bacteria," says Lindner, "but we've found that some solvents influence their behavior, flipping them back and forth." What's more, he notes, "certain patterns of diet may do the same." The group has learned, for instance, that niacin tends to turn up the pumps, stimulating growth of the bacteria. Other nutrients may do the reverse.
Finally, Pathobiotek is working hard to identify antibiotic sensitivity levels in autoimmune patients, a prerequisite for delivering therapeutic treatment at all. Already, the team has discovered that one antibiotic, clarithromycin, is likely to stimulate bacterial growth in most patients. The goal is providing a sensitivity test that would help customize treatment for each and every patient while significantly lowering the risk. One of the most important aspects of Lindner's work could be the finding of bacterial persistence following antibiotic therapy. Many experts contend that autoimmune disease, while perhaps triggered by infection, continues its assault long after the microbes have been killed. But Lindner's findings suggest that autoimmune illness may be driven by persistent infection - when infection subsides, his research indicates, autoimmune symptoms do, too. "I don't know of any way to get rid of this organism," Lindner says. "The best we can do is reduce its levels. We don't know why. We have no proof at this point that they are intracellular and, thus, hidden from antibiotics, but their persistence in the body suggests that may be the case." Another theory, he notes, is that human blood bacteria cross the placenta. If the organisms are present prior to birth, they may not be recognized as foreign by the immune system and, thus, may be especially difficult to clear.
|HBB may not be the long-sought trigger for MS.
WWhen all is said and done, Lindner concedes, human blood bacteria may not be the long-sought trigger for MS, CFS, and other forms of autoimmune disease. "There is always the possibility that the changes in the bacterial level are a secondary effect," he states. "If so, it would still be a significant marker of disease activity. On the other hand, if these organisms are truly causative, sooner or later we will find a means to control them."
Due to corporate restructuring, Pathobiotek will soon be changing its name to Adesy, Inc., and will be moving corporate offices to a different Texas location.
Pamela Weintraub is a former staff writer at Discover, former editor-in-chief of Omni Internet, and the author of 15 books on health and science.
Susan Wolsborn is Web designer of HMS Beagle.
Multiple Sclerosis and Chronic Fatigue Syndrome: A Bacterial Etiology? - an article written by Luther E. Lindner in response to requests for information about his research.
Viruses and Autoimmune Disease: Two Sides of the Same Coin? - examines experimental models on the role of viruses. From Trends in Microbiology, 2001, 9:8:377-381. Full text available from BioMedNet.
The Role of Different Subsets of T Regulatory Cells in Controlling Autoimmunity - focus on the role of T regulatory cells in prevention of autoimmunity and maintenance of homeostasis. From Current Opinion in Immunology, 2000, 12:6:676-683. Full text available from BioMedNet.
Antigen-Specific Therapy for Autoimmune Disease - discusses the paradoxical use of self-antigens as tools for autoimmune disease therapy. From Current Opinion in Immunology, 2000, 12:6:704-711. Full text available from BioMedNet.
Animal Models of Autoimmunity and Their Relevance to Human Diseases - reviews recent advances. From Current Opinion in Immunology, 2000, 12:6:684-690. Full text available from BioMedNet.
Understanding Autoimmune Disease - an online booklet from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Immunology Links - includes worldwide associations, journals, job opportunities, and technical information for immunologists.
National Multiple Sclerosis Society - a gateway to information on MS.
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