Chlamydia pneumoniae: the possible cause of MS?

A forum for the discussion of antibiotics as a potential therapy for MS

Chlamydia pneumoniae: the possible cause of MS?

Postby SarahLonglands » Sat Jun 19, 2004 12:58 pm

My husband started with this posting on the Minocycline thread:

Posted: Mon Jun 14, 2004 7:36 pm Post subject:

A small double-blind trial of antibiotics from the Vanderbilt team has just been presented at a conference:

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,

Ben


then these entries followed:

Hi Ben, Thanks for your post, I checked the net and found this in regards to what you posted :

http://www.ncbi.nlm.nih.gov/entrez/quer ... s=15164186

The "SpringerLink" also goes to a reference..


Me!:
This is my story, as Ben’s wife: I must have had multiple sclerosis for quite a few years, looking back, in the relapsing remitting form, but the relapses were so minor, so far apart and so soon gone, that it never really occurred to me. As soon as I got over each attack I would forget about it and get on with life.

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.


Very interesting to hear from the experiences of Ben and his wife!
I don't know how important it is to further speculate on how these antibiotics work, but I'm a curious person so...


Quote:

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.



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?

/Mac


Me again - sorry!
Forgive me for replying when you asked Ben the question, but I thought it should be obvious that a microbiologist would be more interested in killing germs, chlamydia pneumoniae in this instance. 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.

Anecdote


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.


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.

That might also explain good results of the minocycline study.

-finn


Philip, with one of my husband's on-line papers!
Increased prevalence of and gene transcription by Chlamydia pneumoniae in cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.

http://www.ncbi.nlm.nih.gov/entrez/quer ... s=15164186

-----------------------------------------------------------


Empirical antibacterial treatment of
infection with Chlamydia pneumoniae
in Multiple Sclerosis:

http://www.davidwheldon.co.uk/ms_treatment.html


Arron:
i think this thread has unearthed some VERY important information... we will follow up on this, but PLEASE keep it coming.

thank you to all the participants thus far; we are so thrilled that this kind of information is being published for the world to see.


Today 6/17/04, I had a long conversation with the neurologist for my fiance', we discussed her MS and the current treatement and we also discussed everything I have researched recently from LDN to diet..

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..

Philip


--------------------------------------------


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)


Nancy Humphrey
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."


Then my husband owing up to who he was:
Do antibiotics work because of their antibiotic effect or because of their immunomodulatory effect?

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


Wilson:
I find the lack of response to this post very dissappointing. Rather than post personal attacks against fellow MS sufferers or the NMSS, I am hoping to read some responses from some of the more knowledgeable members.

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?


Greetings wilson, there is some good discussions here and other places about Chlamydia Pneumoniae, and I would not be surprised if this topic has its own section soon as it is so important..

Chlamydia Pneumoniae is not an STD, for more information you can visit my website and under the Chlamydia Pneumoniae section on left, are several section withs info..

Philip

http://members.cox.net/mscaregiver/index.html




Thanks for the link. Sometimes I just can't enough info. Not to sound like the X-Files show, but I believe the "Truth is out there".

I believe I am not the only one who confuses C. pneumoniae as a STD. A google search revealed this info:

"Chlamydia pneumoniae, proposed new name, Chlamydophila pneumoniae. C. pneumoniae is distinct from other Chlamydia species"


Then finally, me again, registered by now!

Hello Wilson,

I am writing this from a rather privileged position, being married to the medical microbiologist who took it upon himself to treat me, once I had been diagnosed with SPMS and told that there was no treatment and I should just wait for the disease to follow its course.

David spent a few days doing some research and decided to start me straight away on the antibiotics mentioned above, not even bothering to get me tested until a few weeks later, because I was degenerating so rapidly. Within just a couple of weeks I showed a marked improvement: my speech, which was becoming slurred, returned to its normal crispness, as did my mental acuity. The physical defects are still improving: I noticed only this week that the grip in my right hand is now nearly as strong again as the left hand and my walking is slowly but surely improving. Then, of course, there is the massive improvement in the MRI scan.

As far as being tested for Chl pn, as you will see from Philip’s previous post:


“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.”


Here we get into the realms of why only some people get MS when nearly everyone gets a Chl pn infection, but that can be another posting!

It is also a rather difficult test to do with any degree of accuracy, so it is probably better to just try to get your MD to treat you empirically. In the posting immediately above yours you will find two papers that you can download and print out to show your MD.

As far as the downside, there really isn’t one if you take the appropriate supplements mentioned in the pdf, especially acidophilus. I certainly have suffered no ill effects. Thrush and candida are often mentioned but I have never had either. In the Vanderbilt trial it has been shown not to be a problem at all.

Best wishes to you and everyone else as a new member,

Sarah

PS: The proposed new name is very sensible to my eyes

So carry on from here...................
Last edited by SarahLonglands on Wed Jul 28, 2004 9:27 am, edited 1 time in total.
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Postby mscaregiver » Sat Jun 19, 2004 3:23 pm

As Oligoclonal bands & oligodendrocyte have been mentioned concerning Chlamydia Pneumoniae, I did some research on the terms to understand them better, also as I was reading I came across an image which I thought was very helpful in visualizing Myelin and several other items.

The link to the image:

http://science-education.nih.gov/nihHTML/ose/snapshots/multimedia/ritn/spinal/wrapping.html

Areas of numeric interest are highlighted in red..


Philip
-------------------------------------------------------------------------



Oligoclonal bands

From : http://encyclopedia.thefreedictionary.com/Oligoclonal%20bands


Oligoclonal bands are a about two to five bands of immunoglobulins. Each band is in a protein secreted by plasma cells. They are found in spinal fluid and blood serum in some persons. They are discovered by testing the fluids on a gel which reveals the bands.
The presence of Oligoclonal bands in spinal fluid often indicates a disease of the Central Nervous System

The human central nervous system consists of the brain and spinal cord. These lie in the midline of the body and are associated with the skull and vertebrae respectively.

The central nervous system along with the peripheral nervous system comprise a primary division of controls that command all physical activities of a vertebrate. Neurons of the central nervous system affect consciousness and mental activity while spinal extensions of central nervous system neuron pathways affect skeletal muscles and organs in the body.
if the bands are not also found in blood serum, however the presence of one band, called monoclonal, is not serious and may be normal. The bands usually disappear from the spinal fluid as a person recovers from the neurological disease.

Approximately 90% of all patients with Multiple Sclerosis have these bands.Multiple sclerosis (MS) is a non-contagious chronic autoimmune disorder of the central nervous system which can present with a variety of neurological symptoms occurring in attacks or slowly progressing over time.


Historical overview
There are a few early reports about patients who could have suffered from MS. St. Lidwina of Schiedam (1380-1433), a Dutch nun, may have been the first reported MS patient. From the age of 16, she developed intermittent pain, weakness of the legs, and visual loss—symptoms typical of MS. She died at the age of 53.


------------------------------------------------

From: http://www.ii.bham.ac.uk/clinicalimmunology/Neuroimmunology/IEF.htm


Neuroimmunology: Multiple sclerosis (MS) - diagnosis aided by the detection of oligoclonal bands (OCB) in the cerebrospinal fluid (CSF).
More than 95% of patients with multiple sclerosis have OCB (2 or more) in the CSF (intrathecal IgG synthesis).

There is no correlation between OCB in CSF and demyelinating process.

OCB can be present even when the CSF IgG level is normal.

Once an oligoclonal response is established, it can be maintained for the natural life of the patient.

OCB have been reported in other cases, for example, neurosyphilis, acute bacterial or viral meningitis, progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, progressive rubella panencephalitis, polyneuritis, optic neuritis, trypanosomiasis, and other infectious or autoimmune diseases.

Interpretation of OCB in isolation is meaningless.

Isoelectric focusing is most sensitive method for detection of the OCB.

Below are OCB patterns which are likely to be seen. The most important pattern of OCB in MS is intrathecal IgG synthesis (blot 2 and 4).
Pictures of Blots on website..

-----------------------------------------------

From : http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12481674&dopt=Abstract

1: J Pak Med Assoc. 2002 Aug;52[8]:351-3. Related Articles, Links


CSF oligoclonal bands in multiple sclerosis.

Siddiqui I, Aleem S, Kayani N, Baig S.

Department of Pathology, Aga Khan University, Karachi.

OBJECTIVE: To study the significance of oligoclonal bands in neurological disorders, specifically in Multiple Sclerosis (MS). METHODS: The study was designed to assess the sensitivity and specificity of the test methodology of CSF electrophoresis by performing the retrospective analysis of CSF samples sent for oligoclonal bands (OCB). A total of 603 samples were received by the Clinical Laboratories, Department of Pathology of The Aga Khan University, during a period of 54 months (January 1993-June 1997). All of these samples were analyzed by performing CSF protein electrophoresis. One hundred thirty three out of 603 samples showed evidence of OCB. Out of these, 24 patients were registered with Section of Neurology, Department of Medicine, The Aga Khan University Hospital. These 24 patients were finally selected for analysis. Relevant clinical details such as age, sex and clinical presentations were recorded. RESULTS: Fifteen (62%) out of 24 patients with positive OCB were diagnosed as cases of MS. Four (17%) patients were diagnosed to have subacute sclerosing panencephalitis (SSPE). Five (21%) patients were having other inflammatory neurological disorders. CONCLUSION: The overall relative sensitivity and specificity for multiple sclerosis were found to be 100% and 62.5% respectively. Lack of specificity was attributed to the fact that OCB were positive in other neurological disorders as well.

PMID: 12481674 [PubMed - indexed for MEDLINE]

------------------------------------------
oligodendrocyte

From: http://science-education.nih.gov/nihHTML/ose/snapshots/multimedia/ritn/spinal/wrapping.html

although specific to spinal cord work, the definitions and picture pertaining to MS areas is very helpful..

excellant picture to help understand areas..

Myelin wraps around a nerve cell axon in the spinal cord. In the CNS, glial cells called oligodendrocytes produce myelin, which is composed of multiple layers of oligodendrocyte membranes that wrap concentrically around one or more axons. (In the PNS, Schwann cells form myelin.) The myelin sheath around an axon acts like an electrical insulator, allowing nerve impulses to be conducted very quickly. Myelin appears white and shiny because the layers of membrane that form it contain large amounts of fatty substances called lipids.
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Postby mscaregiver » Sun Jun 20, 2004 11:36 am

Possible reason concerning oligodendrocytes deteriation ..

From: http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract


Astrocytic beta2-adrenergic receptors and multiple sclerosis.

De Keyser J, Zeinstra E, Wilczak N.

Department of Neurology, University Hospital Groningen, Groningen, The Netherlands. j.h.a.de.keyser@neuro.azg.nl

Despite intensive research, the cause and a cure of multiple sclerosis (MS) have remained elusive and many aspects of the pathogenesis are not understood. Immunohistochemical experiments have shown that astrocytic beta(2)-adrenergic receptors are lost in MS. Because norepinephrine mediates important supportive and protective actions of astrocytes via activation of these beta(2)-adrenergic receptors, we postulate that this abnormality may play a prominent role in the pathogenesis of MS. First, it may allow astrocytes to act as facultative antigen-presenting cells, thereby initiating T-cell mediated inflammatory responses that lead to the characteristic demyelinated lesions. Second, it may contribute to inflammatory injury by stimulating the production of nitric oxide and proinflammatory cytokines, and reducing glutamate uptake. Third, it may lead to apoptosis of oligodendrocytes by reducing the astrocytic production of trophic factors, including neuregulin, nerve growth factor and brain-derived neurotrophic factor. Fourth, it may impair astrocytic glycogenolysis, which supplies energy to axons, and this may represent a mechanism underlying axonal degeneration that is hold responsible for the progressive chronic disability.

Publication Types:
Review
Review, Tutorial

PMID: 15006703 [PubMed - indexed for MEDLINE]
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Postby OddDuck » Sun Jun 20, 2004 6:29 pm

Oh my goodness! Philip! I see what you meant. That's the same article I stumbled across quite a few weeks ago when doing my research!

It was after I started on my "quest", and when I came across that article, I jumped up and down for joy! I wasn't ALONE with my theories. Matter of fact, I was in good company.

Also, folks. I live in Nashville, Tennessee! My next appointment is going to be with the Vanderbilt neuros you are talking about here (Sriram and Moses).

I'm going to take my research to them, also (if my PCP hasn't already given it to them - he's the one who knows them, works with them, and is referring me - my PCP is also a PhD geneticist and also is (or was) a professor at Vanderbilt (and still maintains staff privileges there.) My former neuro came from the Mayo (Moses Rodriguez was his mentor for many years, and Claudia Lucchinetti was his colleague.) He and I had a parting of the ways, though, so I'm heading off to Vandy now.

Anyway.....when I go to see those guys, I'll just ASK them "what's up". Maybe THEY will be more inclined to actually do some testing on me to see what this drug I'm taking is actually doing and how!

This is WAY too coincidental! HAH!

Deb
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Postby OddDuck » Sun Jun 20, 2004 9:03 pm

Oh.....as clarification to my last post, by asking them "whats up", I meant I plan to ask them about minocycline.

It appears that there may be conflicting theories being published about how minocycline DOES help MS....via the "viral" pathway (which doesn't sound correct to me, because of the fact that antibiotics don't affect viruses), the "allergy" or bacterial pathway, or via its inhibition of caspase-3 (an enzyme that is part of the cascade that mediates programmed cell death). My personal thoughts are that minocycline accidentally exhibits it effectiveness for MS as something totally unrelated to its original intended use.

Interesting stuff!!

Deb
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Chlamydia pneumoniae and anecdotal evidence!

Postby SarahLonglands » Tue Jun 22, 2004 7:14 am

Help! I am drowning in a sea of quotes, oligloclonal bands and oligodendrocytes, all of which are all very interesting and important and I know them intimately after the last few months of reading, but I started this thread because I was hoping to draw attention to the ever increasing likelihood that MS is caused by chlamydia pneumoniae, as the success of my treatment surely shows. Of course, it can only be viewed as merely anecdotal, (hence my nickname) but the antibiotics involved are so harmless that surely it is worth harassing your MD or Neuro’ to give it a go, whilst awaiting the larger double blind trial being organised at Vanderbilt. Yes, maybe there are other infective agents involved as well, but they would all be treatable either by the Nashville regime of rifampicin and azithromycin or the Bedford, England regime of doxycycline and roxithromycin.

Of course, there are several other things involved, namely some genetic predisposition and also vitamin d deficiency, which explains why it is so much more common in northern latitudes. Otherwise far more people would suffer from MS, since so many people end up carrying antibodies showing a chronic chlamydia pneumoniae infection. Incidentally, as you get nearer to the equator, the people most likely to succumb to MS are Muslim women and it does not take much to realise why, does it?

The Bedford treatment is strongly anti-inflammatory, but the Nashville regime has been chosen purposefully because it is not. This is why the recent small scale Vanderbilt trial is so important. I was started on doxycycline but then changed to rifampicin, which is stronger, and then sporadic bouts of metronidizole were added for the bactericidal benefits, the aim being to make the eventual course as short as possible.

I will add here a few names and search terms for those of you who are so good at ferreting out information:
Pekko Saiku and chlamydia pneumoniae.
Suramiyam Sriram and Charles Stratton.
Rogier Hintzen and multiple sclerosis
And this, relating more to my experience, bearing in mind that I am the Jane mentioned: www.davidwheldon.co.uk/ms_treatment.html and especially www.davidwheldon.co.uk/cpn-ms.pdf

Now it is gone 15.00 hours in Bedford, so I must get back to work!

Sarah
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Make what you will of this!

Postby SarahLonglands » Thu Jun 24, 2004 3:44 am

Copied from my posting in "Drug Cocktails"

Hello Daunted,

Here is what I take:

rifampicin, 300mg twice a day
roxithromycin, 150mg twice a day (which would have to substituted by azithromycin in the States)
B-12, 5000mcg sublingually every day
co-enzyme Q10 in large dosages
4000mg Fish Oil per day
Vitamins A,B,C,D,E, selenium and magnesium in large dosages
acidophilus, several capsules as required.

Also, five day bouts every three weeks or so of:
metronidizole, 400mg three times a day

10 months ago I could hardly walk unaided or use my right hand due to rapidly progressing SPMS, now I am able to walk without needing even a stick for quite some distance, I can use my right hand relatively easily and my fatigue levels are greatly diminished.

Sarah
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Postby Shayk » Mon Jun 28, 2004 7:52 pm

Hi all--this is another FYI I stumbled onto (no pun intended) :lol: and in a quick glance of the thread I didn't see it referenced previously.

So, here goes, an article from Epidemiology, March 2003 (Vol. 14, No. 2)
entitled Infection With Chlamydia pneumoniae and Risk of Multiple Sclerosis by Munger, KL, Peeling RW, Hernan MA, et al

This is a nested case-control study using the Nurses Health Study and Nurses' Health Study II Cohorts, which include a total of approximatley 61,000 women. There were 141 incident cases with definite or probably multipole sclerosis (MS). The frequency of positive serology for Chlamydia pneumoniae was significiantly associated with MS with an odds ratio of 1.7 Further, the geometric mean titers were positively associated with progressive MS. The authors conclude that their study supports a positive association between C pneumoniae infection and progressive MS.


Presumably that's the abstract. The info here is from www.medscape.com/viewarticle/456574_9

I think you have to register for Medscape, but it's free. I didn't have time to try and get the full text, but hopefully this is enough for people researching the topic.

To those of you in Europe, the Nurses Health Studies were big US studies (at least I think they were just US Nurses, but I don't really know even that.)

Take care all.

Sharon
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Multiple Sclerosis - Cause Identified?

Postby mscaregiver » Wed Jun 30, 2004 10:02 pm

From :http://www.perlhealth.com/vol4no3.htm#ms

Multiple Sclerosis - Cause Identified?

Multiple sclerosis (MS) is a fairly common and generally progressive disease of the central nervous system affecting some 350,000 Americans. While typically regarded as simply a cause of morbidity, more than 3,000 Americans die each year as direct consequence of MS - a disease in which the cause has remained stubbornly elusive.

Over a century ago, French physician Pierre Marie, published a monograph in which he indicated that multiple sclerosis was likely caused by some form of infection. Indeed by 1998, at least 16 infectious agents had been identified as possibly causing multiple sclerosis. Under strict scientific scrutiny, none of these infectious agents has been found to specifically induce the disease.

But recently, the most convincing data ever presented relating infection with a specific organism to multiple sclerosis has been reported from the department of neurology and pathology, Vanderbilt School of Medicine, Nashville, Tennessee. Dr. Subramaniam Sriram and co-workers, publishing their results in the July 1999 issue of Annals of Neurology, have demonstrated the presence of a specific type of bacteria in 100% of the 37 multiple sclerosis patients they studied. As the authors reported, “the evidence of Chlamydia pneumoniae in both progressive MS and relapsing - remitting patients suggests that the infection of the central nervous system with Chlamydia pneumoniae occurs early and persists perhaps throughout the course of the disease and does not differentiate between different clinical subtypes of the disease”.

This organism, Chlamydia pneumoniae, is a fairly recent addition to the list of bacteria known to affect humans. It is now recognized as a cause of pneumonia, pharyngitis, bronchitis, and several chronic diseases. More importantly, Chlamydia pneumoniae has now been recognized as playing at least some positive role in reactive arthritis and coronary artery disease - medical conditions which, like MS, are characterized by ongoing inflammation.

An interesting observation supporting the relationship between Chlamydia pneumoniae and multiple sclerosis is based on the discovery that two commonly used medications for multiple sclerosis, interferon-beta and methotrexate profoundly inhibit the growth of the Chlamydia bacteria. This is interesting and provocative information as we do not yet fully understand why these drugs are sometimes effective in MS treatment.

Over the past several years, the medical literature has published various articles describing specific viruses thought to be the causative agent for multiple sclerosis, only to have these reports subsequently refuted. But this new research describing the possible relationship between Chlamydia pneumoniae and multiple sclerosis is most compelling. And the good news is that unlike viruses, specific antimicrobial medicines are available to treat Chlamydia pneumoniae.

Based upon this research, it is not unreasonable for patients with multiple sclerosis to consider an empiric treatment for Chlamydia pneumoniae. As this discovery is so new, no specific treatment protocols have as yet been created and it will likely be several years until clinical trials have been designed, approved, funded, completed, and ultimately published, until we know for sure that MS patients should be treated. But in light of the present evidence, empirically treating MS patients for Chlamydia pneumoniae seems reasonable. Obviously this decision should be discussed with treating physician. Antibiotics generally quite effective in treating Chlamydia pneumoniae infections include doxycycline and tetracycline. Doxycycline may be the more effective treatment since it is more able to penetrate the blood - brain barrier to enter the brain.

By: David Perlmutter
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Postby SarahLonglands » Thu Jul 01, 2004 3:34 am

This is a good find, although David Perlmutter is a bit out of date, since the latest Sriram study was presented to the American Academy of Neurologists scarcely a couple of months ago. This was a very small study involving just eight people and very strict parameters, lessening other people criticizing the results simply because they can't isolate c pneumoniae themselves. It can be found fairly easily by doing a search on Sriram and the Academy. A much larger scale trial is now planned, but quite a few people are now treating patients empirically, including Sriram and Stratton in Nashville and David Wheldon in the UK. The results are astonishing. (Says one of the living and breathing results)

Sarah
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Postby mscaregiver » Thu Jul 01, 2004 3:41 am

Hi Sarah, yes it is older, but sometimes looking back can help verify the future :-)
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Postby SarahLonglands » Thu Jul 01, 2004 4:35 am

Hi Sarah, yes it is older, but sometimes looking back can help verify the future


Very true, Philip!!
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Postby OddDuck » Thu Jul 01, 2004 4:55 am

I posted this on another thread, but thought maybe it should go here, also.

Again, as I mentioned before, my next appointment is with the Sriram team at Vandy, so I do plan on discussing C. pneumoniae with them.

Deb
*************

Most all of these "new" discoveries pertain to treating RRMS or beginning stages of MS, not the progressive forms.

You may find this interesting:

Deb

*************************************

MS Cause Discovered? updated 5-11-04
In regard to the double blind study of antibiotics on MS:

The latest news on Chlamydia pneumonia

From Dr. Sriram of Vanderbilt University, Discoverer of Chlamydia pneumoniae in MS.

Dear Mr Miller.

Although the patients that I have treated with antibiotics have been about 20-25, the results have been varied. In short, individuals who have been treated earlier in the course appear to do better than those treated later. However there is not a scientfic study by any means. The study that is funded by the MS is underway and we have enrolled 11 patients into a double blind study.

Unfortunately this is a double blind placebo study, that is what the reviewers wanted to have done; now it has become very difficulty to recruit patients into a placebo controlled study since not many want to be in a placebo arm. This was supposed to be a two center study but South Western Univ at Dallas have dropped out because of their inability to recruit patients. They did not get a single patient into the study. I have therefore been scrambling to get other center and two others have agreed to get on. but they have not recruited any patients yet. So that is where we are.

My hunch is that as the disease becomes progressive, number of organisms decreases and therefore they become more difficult to be tracked down by antibiotics. I believe this may be the reason that the relapsing remitting disease patiens appear to do better than the progressive. Or they may need a different regimen of therapy. All this needs to be sorted out.

I hope I have answered your questions but let me know if you need any more info.

Sincerely,

Ram Sriram
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Postby OddDuck » Thu Jul 01, 2004 5:03 am

Sorry....here's just another quick something. (I don't want to put a damper on ANY hope for finding a cause, I just hope folks won't get overly excited, either. Disappointment is harsh.)

Deb
*************************

Chlamydia & MS

Nancy Humphrey

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."

***************************

http://www.mult-sclerosis.org/news/Nov2000/DoChlamydiaPneumoniaeandHHV6CauseMS.html

***************************

Evidence for infection with Chlamydia pneumoniae in a subgroup of patients with multiple sclerosis.
Layh-Schmitt G, Bendl C, Hildt U, Dong-Si T, Juttler E, Schnitzler P, Grond-Ginsbach C, Grau AJ.

Ann Neurol 2000
May;47(5):652-5

Department of Microbiology, University of Heidelberg, Germany.

In a pilot study, we identified Chlamydia pneumoniae in the cerebrospinal fluid by polymerase chain reaction in 5 of 10 patients with definite multiple sclerosis (MS). In a second series, 2 of 20 patients with definite MS and 3 of 17 patients with possible/probable MS or MS variants, but none of 56 patients with other neurological, diseases were polymerase chain reaction-positive. We confirm that C. pneumoniae can be found in the cerebrospinal fluid of MS patients, but our rate of positive results is lower than in a recent report.

----------------------------------

Other publications on C.p. and MS:

Treib et al. Multiple sclerosis and Chlamydia pneumoniae. Ann Neurol 2000 Mar;47(3):408; discussion 409-11.

Heinzl S. Chlamydia, atherosclerosis, asthma and MS. Med Monatsschr Pharm 2000 Feb;23(2):37.

Boman et al. Failure to detect Chlamydia pneumoniae in the central nervous system of patients with MS. Neurology 2000 Jan 11;54(1):265.

Stratton CW, Mitchell WM, Sriram S. Does Chlamydia pneumoniae play a role in the pathogenesis of multiple sclerosis? J Med Microbiol 2000 Jan;49(1):1-3

Sriram et al. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann Neurol 1999 Jul;46(1):6-14

Sriram S, Mitchell W, Stratton C. Multiple sclerosis associated with Chlamydia pneumoniae infection of the CNS. Neurology 1998 Feb;50(2):571-2
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Anyone have bad results with minocycline?

Postby Byron » Wed Jul 07, 2004 9:08 am

Is there anyone who tried minocycline and it didn't have any results on your MS? I hear a lot about people talking about it working very well, but it would be interesting to know if there are any negative results.
:?:
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