Don't know if you remember when researchers first reported that Chlamydia Pneumae could be a triggering factor of Multiple Sclerosis. A case report where a man with severe MS was treated for a Chlamydia infection with an antibiotic drew a lot of attention in media. The man was progressing rapidly, but when put on antibiotics he went into remission immediately. Doctors and researchers soon thought that MS must be connected with the chlamydia bacteria. The clamydia trace has up to today not resulted in much, but it might be of interest to notice that the man was treated with a common choice of antibiotics when dealing with Chlamydia: Minocycline.
Sriram, S., Song, Y., Moses, H., Stratton, C.W., Wolinsky J.: A pilot study to examine the effect of antibiotic therapy on MRI outcomes in relapsing remitting MS. Poster Presentation. Presented at the Annual Meeting of the American Academy of Neurology, San Francisco, CA, 2004.
A regression of lesions was found in treated patients. Antibiotics reduced the level of parenchymal brain shrinkage to rates seen in the unaffected population. The trial was small but fastidious. Interestingly, the antibiotics they used (rifampicin and azithromycin) don't have the anti-inflammatory properties which minocycline and doxycycline do.
There has been a very interesting paper recently published which found that Chlamydia pneumoniae was actively metabolizing in the CNS of patients with MS, and was actively making a protein, hsp60, which is thought to be highly antigenic and implicated in the autoimmune aspects of MS.
Dong-Si, T Weber J et al. Icreased prevalence of and gene transcription by Chlamydia pneumoniae in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis. J Neurol 2004 May 251(5):542-547
My wife had very early secondary progressive MS. A combination of doxycycline and roxithromycin stopped the progress in a matter of days. That was ten months ago; since then no negative CNS events.
with best wishes,
Things suddenly took a turn for the worse a couple of years ago though, when what was thought at the time to be a minor viral infection left me hardly able to walk across the room, with legs numb from the knees downward and severe vertigo. This somewhat cleared up after a number of weeks, but by no means completely. Then a major gynaecological operation a year later so traumatised my system that I began an inexorable downward spiral. I was living in a kind of mental fog, not even realising how bad I was getting, or even that I had the wretched disease in the first place, until my first MRI scan and resultant diagnosis by a neurologist brought it home to me, in August last year: “secondary progressive multiple sclerosis. There is no treatment and no cure, so go home and find out what you can about the disease, see the MS nurse and then I will make an appointment to see you again”. This is not what an artist who had only recently finished the biggest commission so far in her career wants to hear, especially when she suddenly finds she has lost the use of her painting hand. Over the next few days I was completely distraught, thinking that I would probably never be able to paint again. What could I do? I began to realise that I was going so rapidly downhill and would soon have need of a wheelchair and worse. Well, I never did need that wheelchair or go to see the MS nurse and this is why:
In the ensuing week, my husband, who is a consultant medical microbiologist, set to work, using that most wonderful of modern inventions, the Internet. When still training, he had often thought that the people with multiple sclerosis he saw when studying neuropathology were suffering from an infection. This had been first thought of over a century ago, by the French neurologist Charcot, but had been forgotten in the intervening years when no one could decide what the infection was. Much more recently a new pathogen has been discovered: chlamydia pneumoniae. Within a few days he discovered enough information to decide to put me on a long course of antibiotics: doxycycline and roxithromycin, which hold the pathogen in its intracellular form, then metronidizole, in pulses of five days at a time, as the bactericidal treatment. The course is long and arduous, for certain, but the results are remarkable. Before Christmas I was painting again, although I must admit that for the moment I don’t have the strength or energy to tackle a large oil painting. Back in August, though, I could barely hold a paintbrush, never mind do anything with it. Now I can tackle a more than creditable full-page watercolour, and am getting more strength back by the day.
The best news of all since it applies to everyone, not just an artist put out by finding that she was unable to paint and who thus lost her means of making a living in one fell swoop, is that I had a second MRI scan a couple of months ago. The results of this were completely unexpected by the radiologist, who came rushing out of his room to show us the results. Not only were there no new lesions at all, but also the vast majority of the existing lesions were vastly diminished in both intensity and size. This is not the normal course of events even with people with only relapsing remitting MS, where there is a constant state of flux even when nothing shows on the outside.
I don't know how important it is to further speculate on how these antibiotics work, but I'm a curious person so...
You apperently suggest that the antibiotics like minocycline, azithromycin and rifampicin work by its antimicrobal actions. I'm aware of that earlier on minocycline was thought to work in MS/EAE by its antiinflammatory actions. However, recently much focus has been given to the neuroprotective properties of minocycline. Also rifampicin is suggested to have neuroprotective properties in a recent report by Yulug B et. al. where "rifampicin showed a significant neuroprotection after cerebral ischemia". (However this report seems to be the only one supporting this, so far) So what are your view on this? What is the most likely trace here: neuroprotection or killing germs? What do you think?A regression of lesions was found in treated patients. Antibiotics reduced the level of parenchymal brain shrinkage to rates seen in the unaffected population. The trial was small but fastidious. Interestingly, the antibiotics they used (rifampicin and azithromycin) don't have the anti-inflammatory properties which minocycline and doxycycline do.
An australian study suggests that the formation of active lesions is triggered by the death of nerve cells. A neuroprotective agent could prevent cell death. No dying nerve cells, no active lesions.Anonymous wrote: Neuroprotection does not lead to a massive shrinkage of active lesions in a person with SPMS, but you maybe didn’t notice that part of my posting.
That might also explain good results of the minocycline study.
When I mentioned Chlamydia pneumoniae he immediately responded that the Vanderbilt group is "extremely" excited about the work in this area.
Below are two references I found after our conversation, The article on the work of Dr. Subramaniam Sriram is several years old, but I plan on calling to see if I can aquire an updated report on his work, or possibly find it online..
From : http://www.med.wayne.edu/Scribe/scribe0 ... rigger.htm
Bacterial Genomics Reveals MS Trigger
While at WSU, Derek Lenz studied the bacteria Chlamydia pneumoniae
Infection with a common bacteria could be the switch that turns on the autoimmune response in multiple sclerosis (MS) according to the findings of Wayne State University PhD graduate, Derek Lenz, now of the Scripps Research Institute in La Jolla, Calif. He described the work he carried out as part of Robert Swanborg’s team at Wayne State University School of Medicine. He said studies in rats show that an antigen found in the bacteria Chlamydia pneumoniae mimics part of a myelin protein in the animal’s central nervous system. When injected into the animal, it provokes the immune response that causes the rodent version of MS, experimental allergic encephalitis.
Scientists have theorized for years that MS might be caused by an infectious agent, according to Dr. Lenz. An early suspect was the measles virus, but it was impossible to use the virus to precipitate out the aggregations of auto-antibodies, known as oligoclonal bands, typically found in the cerebrospinal fluid of MS patients. “So that idea kind of went by the board,” he said.
But there was strong evidence from epidemiological data that an infection was involved at some stage. An outbreak of MS in the Faroe Island occurred shortly after World War II – “that strongly suggests that the troops brought some sort of pathogen with them,” Dr. Lenz said.
Lenz’s colleague, Alan Hudson, analyzed the pattern of the main outbreak and three subsequent outbreaks of gradually decreasing severity. He found that the events fitted exactly the pattern of C. pneumoniae infection in the population. “He tried every way possible, but there was no way that he couldn’t make them fit,” Dr. Lenz recalled.
However, C. pneumoniae may seem an unlikely cause of MS – it is a ubiquitous pathogen and, by the age of 70, nearly everybody will show a positive blood test. It causes silent epidemics of bronchitis and low-grade respiratory infections. When not infecting the cells of the lungs, it survives as a spore that is metabolically inert and almost impossible to destroy.
Yet, evidence that the bacteria cold be involved in the disease came from the Subramaniam Sriram’s team at the Vanderbilt University Multiple Sclerosis Center in Nashville, Tenn. He previously reported that 97 percent of MS patients had evidence of C. pneumoniae infection in the central nervous system, compared with only 16 percent in patients with other neurological diseases.
More importantly, Chlamydia antigens precipitated out of the oligoclonal bands. “That’s an amazing result – nobody had been able to do that before and the existence of these bands has been known about for more than 60 years,” Dr. Lenz said.
Now Dr. Lenz and his colleagues have taken the work a stage further. By searching through the chlamydial genome, they found a region coding for a protein fragment that closely resembled the MBP 68-86 region of the myelin protein known to be the main target in EAE. Both peptides were found to activate the T cells that stimulate the encephalitis response, and affected rats showed similar signs of disease.
Dr. Lenz accepts that infection is not the whole story, as there is strong evidence for a genetic component to MS. Women originating from Northern Europe have an exceptionally high incidence, and Seattle and Minneapolis - two US cities with large populations of Scandinavian immigrants - are both disease hot spots, he says.
Nor is it likely that C. pneumoniae is the only infection that can provoke the inflammation that leads to MS. "I don't necessarily think that Chlamydia is the sole etiological agent - I would say that the disease process is the end of many different beginnings," Dr. Lenz concluded.
From : http://www.mc.vanderbilt.edu/reporter/?ID=780
Pneumonia, MS link investigated
April 23, 1999
Dr. Subramaniam Sriram is probing the relationship between certain pneumonias and multiple sclerosis. (photo by Donna Jones Bailey)
Researchers in the Vanderbilt Multiple Sclerosis Center are exploring the relationship between a common organism responsible for community-acquired pneumonias and Multiple Sclerosis.
The Vanderbilt research focuses on the role of Chlamydia pneumoniae, also known as C. pneumoniae, believed to be the cause of 20 to 30 percent of cases of pneumonia in a community setting, in the development of MS.
"The idea that infection may be a cause of MS is not a new theory and stems from the fact that an environmental cause of the disease has been known by a number of indirect evidences," said Dr. Subramaniam Sriram, William C. Weaver Professor of Experimental Neurology and director of the Multiple Sclerosis Center.
Sriram will present his findings on April 23 at the American Academy of Neurology meeting in Toronto.
Previously, researchers have looked at a virus as the infectious agent that may cause MS.
"That has never panned out," Sriram said. "The clinical and pathologic presentation is one of a chronic infection. That's why we come back to an infectious cause over and over again."
The new theory is that Chlamydia, a relatively newly discovered organism, may act as a trigger toward the development of MS, Sriram said.
The Vanderbilt research team began to look at Chlamydia two years ago when Sriram saw a patient with MS who had failed non-conventional immunosuppressive and immunomodulatory therapies.
Following discussions with Drs. Charles W. Stratton, associate professor of Pathology, and William M. Mitchell, professor of Pathology, he decided to explore the chance that a Chlamydia agent might be responsible for MS.
"We explored this in this one gentleman and were successful in culturing the organism," Sriram said. "He subsequently made a fairly dramatic recovery from his MS with long-term antibiotic therapy."
However, Sriram said it is too early to make the assumption that the antibiotics made a difference in the man's illness.
"Extreme caution should be exercised in making causal associations between anecdotal success and what the disease does as part of its natural course. Since MS is known for its spontaneous remissions it is difficult to conclude in one patient that the antibiotics he received was responsible for his recovery. However, in his case, the improvement was so dramatic that we decided to explore the issue further."
Armed with a pilot grant from the National Multiple Sclerosis Society, the Vanderbilt research team has studied a more extensive group of patients over the past two years. The organism was found in the central nervous system of a majority (90 to 95 percent) of the MS patients who were tested.
Evidence from a number of angles points to the presence of Chlamydia, Sriram said.
"This observation is interesting and is breaking new ground for a number of reasons," Sriram said. "Even when other associations with viral organisms have been entertained, the degree of association has never been so high as with Chlamydia pneumoniae. We can demonstrate the evidence by a number of means - by culture, or by PCR techniques -- that show there are antibodies to this organism present in the spinal fluid of these patients," he said.
The Vanderbilt research has also shown that the organism is present early in the disease course and appears to persist.
The next step is a larger study, sponsored by the National MS Society, to be conducted over a three-year span.
"We will be studying 50 patients and prospectively following them over three years," Sriram said. "We will be looking at the brains of MS patients who have died from the disease or in whom a brain biopsy was done to show the presence of the organism," he said, adding that preliminary evidence in autopsies of MS patients who have died from other causes shows the organism can be detected in the brain.
About one-half million people in the United States have MS. There are about 2,000 patients in the Middle Tennessee area. About 1,200 of those patients are seen at the Vanderbilt center.
Sriram said the research may show that Chlamydia may not be directly responsible for the disease.
"Many people believe MS is an autoimmune disease and that the organism may initiate an immune response that goes ahead and does the damage although the organism itself does not secrete any toxin or harmful compounds. The disease may be the inadvertent injury in the body's attempt to get rid of the organism."
Sriram said he is "cautiously optimistic" about what answers the research may provide.
"It's just too early to say," he said. "Given the fact that the history of an infectious etiology has been very difficult to prove in the past, and prior organisms that were entertained as potential candidates have not been proven to be the cause, enormous caution needs to be exercised in showing the relationship between the organism and the disease before Chlamydia pneumoniae can be directly implicated as a causative agent in MS."
It has long been thought that the basic process in MS is 'rogue activity by microglia' which attack the myelin. A very recent paper Barnett, MH and Prineas, JW, Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion, Annals of Neurology April 2004, Vol55 No4 pp458 - 468 shows that the first visible phenomenon in the newly forming lesion is mass local oligodendrocyte cell-death. Demyelination and inflammation are secondary to this. This is an important breakthrough.
Antibiotics probably work principally by their action against Chl pneumoniae, but may also help in reigning in microglial activity against the degenerating myelin caused by oligodendrocyte loss, thus breaking the cycle of auto-immunity.
What causes oligodendrocyte cell death? Probably antibodies to bacterial hsp, as shown in the paper I referenced earlier. Oligodendrocytes are known to undergo apoptosis (cell-death) in the presence of antibodies to hsp60 and hsp90. See Cid C, Alvarez-Cermeno JC, Camafeita E, Salinas M, Alcazar A. Antibodies reactive to heat shock protein 90 induce oligodendrocyte precursor cell death in culture. Implications for demyelination in multiple sclerosis. FASEB J. 2004 Feb;18(2):409-11. Epub 2003 Dec 19.
On seeing my wife's response to antibiotics, and the improvement of the repeat MRI scan, I can commend a trial in those who have RRMS and SPMS which is still progressing. Have a look at my webpage http://www.davidwheldon.co.uk/ms_treatment.html and a recently updated review in pdf format http://www.davidwheldon.co.uk/cpn-ms.pdf
David (Ben) Wheldon
To get some relief from the MS monster, could it be as simple as take antibiotics orally? I mean, MS is associated with needles and pain, and dealing side effects that are overwhelming.
What is the next step in order to investigate further this type of treatment? Do we go to our MD to get tested for Chl pneumoniae? What is the downside for taking these antibiotics? I thought Chl pneumoniae was a STD. Is it possible to contract it in other ways?