Multiple Sclerosis and the CPn model

Multiple sclerosis is a disease of the central nervous system thought by most to be autoimmune because it is clear that the nervous tissue is being damaged and that also the immune system is present at the actual lesion location. Efforts to find a germ that the immune system is attacking have fallen flat with conflicting and inconclusive results. We propose here that MSi may be caused by chlamydia pneumoniae (CPn). In this book page I will outline the various findings in research on MS and also findings on CPn highlighting similarites.

While it is very interesting material, the reader must understand that this is a theoretical model and I am coming at it with this point of view, "If CPn causes MS what does this research mean?" I do have a bias as I begin. But I offer this to you, the reader: Everyone has a bias, I am just stating mine up front. The pharmaceutical company that is making a drug to suppress your immune system comes at the issue from a bias that MS is autoimmune, even though this is not proven but a model. So, we will start there.....

MS:Is it autoimmune?

Most of the medical community thinks MS is autoimmune because every damaged area in the MS brain has immune system cells present. Or do they? In 2004, Prineas and Barnett rocked the MS world with their paper "Relapsing and remitting multiple sclerosis: pathology of a newly forming lesion" found HERE<

As you can see in that paper, and I was lucky enough to read the whole citation, the notion that the immune system comes in and damages the nerves is seriously questioned. Essentially these authors found that in autopsied brain tissue, the brain had the lesions that they expected with immune system cells present, but these tissue samples ALSO had NEW lesions in which the nerve had died, but the immune system had not yet gotten there to clean the area up and remove the dead tissue. How can the immune system have caused the injury if the injury occurs before it arrived? If we understand that immunity includes cleaning up dead cells and unwanted tissue, we see there is a very good reason for the immune system to be present in the brain if a nerve has died from some other cause.
In fact this is a very logical reason for the immune system to be present because we already know that the immune system works this way naturally, this is what it is designed to do. All other theories from molecular mimicry to autoimmunity require that the body made a mistake and began attacking itself.

This work is supported by review of the issue written by Chaudhuri and referenced on pubmed HERE< I have been fortunate enough read this paper (the link I provide here has a "blank", you'd have to subscribe to read it) and this author is adament that MS is not autoimmune,. In an earlier paper he said;

"Multiple sclerosis (MS) is a common, disabling neurological condition whose pathogenesis is not clearly understood. Although current treatment recommendations assume an immunopathogenic disease mechanism, MS may not be an autoimmune disorder. Long-term immunological therapy for MS is in our view an untested approach, guided by uncritical acceptance of data from drug trials. We do not believe that there is convincing evidence that any of these immune-based treatments prevents long-term disease progression, or has much effect on common disabilities such as fatigue, pain, depression and cognitive impairment. The recent recommendations of the National Institute of Clinical Excellence did not address important issues regarding disease modification, management of paroxysmal symptoms and the likely therapeutic candidates for future treatment trials. We discuss treatment options for MS beyond the NICE guidelines" (Chaudhuri 2005) reference HERE<.

A recent work by Dr Sriram of Vanderbilt University published in the Annals of Neurology and referenced HERE< indicates that MS is utterly different on a cellular level than EAE which is a pure autoimmune disease. There are different cytokinei upregulations and a cellular immune different profile altogether, which is a critical issue because the therapies generated by looking at what impacts EAE are geared to alter these cytokines. He contends that the constant reliance on this model as a "good model" of MS and through which all treatments are brought to us limits research understandings about what MS really is. In essence we are treating EAE not MS when we bring new protocols and strategies to market via this method. It is interesting to note that EAE is curable and it has been so for decades via the same medications that do not actually help people with MS.

is yet another abstract indicating that anti-inflammatory approaches may be misdirected in MS. Importantly, these authors say that even the newer immune suppressing approaches, while they do result in a large decreases in MRI activity, do not result in an improvement in disabiilty long term. Quote;

"Suppressing relapses by disease-modifying agents does not dramatically influence the progression of irreversible disability. Interferons beta reduce the relapse rate by 30% and conventional MRI activity by more than 50%. In spite of this effect on inflammation, the effect on disability is only marginal and possibly relapse-reduction-dependent. Administration of Campath-1H to patients with very active disease in terms of frequency of relapses, accumulation of disability and MRI activity, results in a profound, prolonged lymphopenia and the suppression of clinical and MRI activity, but in spite of this, clinical disability and cerebral atrophy still progress. The same experience has been reported with cladribine and autologous haematopoietic stem cell transplantation..." copied verbatim
The paper suggests that neuro regeneration and protection should be the main focus of MS strategies, not simply reducing inflammation. It also raises an important question for medicine in general in regards to currently available therapies, namely exactly what does reduction in inflammation accomplish for the MS patient and at what cost?

So here I have presented the idea that MS is not autoimmune and offered research that caused me to form that opinion. So, If MS is not autoimmune but instead a disease in which the nerves die for some reason then the immune system comes in to clean up the debris just as it is supposed to, what bacteria or virus is to blame?

The infective model of MS

The infective model of MS is the notion that MS is caused by a virus or bacteria. While numerous attempts have been made to isolate the infective organism, unfortunately no one organism has been consistently tied to MS. Several of the possibiities are human herpes 6 (roseola), epstein barr virus (mono or glandular fever), and pleomorphic bacteria like chlamydia pneumoniae, borrelia, and mycoplasma. While there are articles outlining some people finding and isolating each of these things in the MS brain, others do not find the same organism. Here in these pages we are presenting the idea of CPn as the possible infective organism but it may be that the kinds of changes we see in CPn could be common to changes seen in other bacterial infections like persistant borreliosis and potentially even viral causes. The body often uses the same strategies to do multiple things as in, for example, creating a fever in both viral and bacterial infections of many kinds. We are investigating CPn specifically here as the theoretical cause of MS because Vanderbilt University research finds CPn in higher numbers in the CFSi of people with MS. Additionally, there is a lot of general research on CPn indicating it is causing a variety of chronic illnesses because it has the ability to change forms and invade the cells themselves including especially immune cells, nerve cells, vessel walls, lung tissue, and blood cells. For example, CPn is considered an emerging pathogen in atherosclerosis. See the CDC link HERE< It is also implicated in asthma, and some authorities such as Margaret Hammerschlag MD of the CDC are now saying that asthma, long thought to be a chronic illness of unknown pathology which has decades of research looking at genetics and other putative factors as causal, is in fact probably a chronic infection with CPn. When discussing MS specifically, it is less clear at this point although there is a lot of circumstantial evidence for CPn possibly playing a role as well as the research done at VU finding it directly.

The first people to produce work that shows CPn in the MS brain were at Vanderbilt University Sriram, Stratton and Mitchell. The first paper is here<. This paper is the whole citation, and it is an incredible privilege to have this paper available to us. This was reprinted on with permission. In essence, the upshot of this article is that using their techniques, the team at VU found evidence of CPn in the vast majority of MS patients. It is important to note that the team used PCRi analysis, CSF immunoglobin IgG reactivity with CPn antigens and culture to evaluate the presence of CPn in these MS brains. People who produce work counter to this frequently offer a single test ie "we cultured the CSF for CPn and found none." Such "opposing" research simply does not have the authority that the original work did due to the lack of diligence. We will investigate this specific issue in depth in the next page about the debate.

Other researchers all over the world have also found CPn in MS brains. A list of some of these follows:

HERE< is a paper by Contini C, et al titled "Cerebrospinal fluid molecular demonstration of Chlamydia pneumoniae DNA is associated to clinical and brain magnetic resonance imaging activity in a subset of patients with relapsing-remitting multiple sclerosis". This paper found that CPn was associated with MS more often if the disease was active on MRI and if RRMSi. Again this author used several detection methods. But in this paper they also found CPn in people with other neurological diseases as well, suggesting it may be able to cause several problems. This might be compared to e.coli causing a bladder infection, urethritis, or nephritis. All are urinary tract infections with slightly different locations and problems.

HERE< is a link to an abstract by Dong-Si T, et al titled "Increased prevalence of and gene transcription by Chlamydia pneumoniae in cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis". This author again found that other neurological diseases also had increased CPn, but that in MS patinets there was increased gene trascription of CPn indicating it may be more active for them.

HERE< is a link to an abstract by Sotgiu s, et al titled "Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis and neurological controls.". This author found CPn in the MS patients only, as different from others.

HERE< is a paper by Fainardi E, Et al titled "Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms" in which an association between CPn and MS was found. The conclusion was "These findings confirm that the presence of a humoral immune response to C. pneumoniae within the central nervous system (CNSi) is not selectively restricted to MS, but is shared by several inflammatory neurological conditions. In addition, our results suggest that an intrathecali production of C. pneumoniae-specific high-affinity IgG can occur in a subset of patients with MS progressive forms in which a C. pneumoniae brain chronic persistent infection may play an important pathogenetic role."

This is a sample of the work that found CPn in MS. To read more simply click one of the links and enter "multiple sclerosis chlamaydia pneumoniae" in the search box on pubmed. You'll get a whole list. Of interest note that this work is done all over the world and a considerable amount of it is done by infectious disease specialists and pathologists, not necessarily neurologists. There is other work, of course, that did not find it since this is how science works to advance understanding. For the best review of the debate on the potential for CPn to be the causitive organism in MS is found in David Wheldoni's site. There is a greater number and a more in depth evaluation of studies there. HERE<. The question "how do we evaluate these controversial findings?" is tackled on the Great Debate page.