Hello, if you have come to this page you are probably investigating this protocol and you are looking for as much information as possible. This page is not here to discourage people but to be honest in offering a more balanced picture, though I am stating up front that I am biased towards this model.
Every approach has limitations. In the field of MSi, even the traditional approaches have one: the autoimmune model remains unproven. Even so many pharmaceutical companies and doctors treat based on this model anyway. In a situation where something must be done for the patient or you may watch them slip away, this may be fine. But one of the biggest complaints I have against the traditional approach is the lack of honesty about this limitation and the unwillingness to discuss it with you, the person who needs treatment.
We want you to understand that the CPn/MS model has limitations as well in the interests of full disclosure and healthy scientific self-examination. These arguments may be mostly of interest to the scientifically minded and should not discourage anyone from considering this approach. But we believe you should know the scientific realities as part of your considerations. It is not a sure bet, partly because it has not been done with hundreds of MS patients so that statistics and clarity about who should be treated this way and who should not are not known. It appears clear from cases reporting here that some people experience changes dramatic enough to change EDSSi scores and cause some reversal of lost function. The limitations on this page also apply generally to treatment with CAPi for other diseases as well.
If you have read all the other pages in this section of the handbook on MS; Multiple Sclerosis and the CPn Model, Smoking Guns, Cellular Similarities between CPn and MS, The Great Debate and The Brain on Pathogenic treatment, you are well versed in the model we use here as a guide for treatment. It is a very good model with many reasons to think CPn is possibly the cause of MS. The question then becomes is it possible that there are any limitations to this model? Is it possible that it could be incorrect?
It is possible and this is where the limitations are.
1. It is not known if all people with MS have this kind of MS or not.
Pneumonia can be caused by a virus, a bacteria, a chemical, or even smoke inhalation. Obviously, if someone had viral pneumonia, antibiotics, which treat bacteria, would only play a supportive role in healing by preventing any bacteria from taking advantage of the already inflamed tissue and becoming a secondary issue. The actual cause of the pneumonia in that case would need to heal on its own, or possibly be treated by using antivirals.
In the same way, more than one trigger might be cause MS. If this is true, there will be some people for whom treatment works perfectly and others for whom it does not and there is no way to know ahead of time which group you would be in.
2. There is no standard lab test and no standard primer used in the MS/CPn research.
This means that many researchers use in house tests-- tests that they developed themselves. Obviously every standard test at one time was someone's in house test so this is not a criticism in and of itself, but it does mean that the research from one worker to another is not necessarily looking at the same thing. It also means that other acknowledged CPn experts in the field do not necessarily agree that "x" researcher using his in house test and who says CPn is there actually was testing for CPn.
Margaret Hammerschlag MD who is a CPn researcher says the VU work was looking at and amplifying human genetic material not CPn. VU says the supposed "clean" primers MH used to make that determination from the lab supply were themselves infected with CPn, so it was CPn they were finding not human. Other labs in other places using OTHER tests also said CPn was present in MS patients, and still others said no CPn in MS. The fact the VU team has been working on this specific issue (rather than CPn in general) for over 10 years gives them added credibility in my mind, but the fact remains that this is unresolved and there is no agreement as to how to detect cryptic CPn.
In regards to MS and the possibility that CPn is the root cause, this means that the research looking at that issue is not necessarily authoritative and the findings must be considered "preliminary". This is true for BOTH sides of the debate, those who find it AND those who do not.
This ties in to the first issue as well since it means that we can't know who to treat and who not to treat. If we had a generally accepted lab test for cryptic CPn that issue would be solved. Another route for proving that CPn causes MS is if researchers use autopsied MS brain tissue and look directly and specifically for CPn in lesions.
Until there is a test that is universally considered reliable for cryptic CPn infection, we are in a place of assessing the model for its circumstantial support. There is a large body of research on how CPn behaves in the body and about the difficulties finding it in cryptic states, which seem to fit nicely with MS. The model makes sense on many levels, but it remains unproven at this time.
3. It is possible that CPn is a bystander, a secondary infection that moves in to the MS brain potentially making the "real" cause of MS more complicated than simply a bacterial cause.
This might be compared to a person with cystic fibrosis, who has very thick secretions in the lungs due to this genetic defect, getting a bacterial pneumonia in addition to the primary disease process. The bacterial process has sinister implications for the person compromised in that way. Treating the bacteria will allow them to return to being relatively stable, but the underlying disease process is still there. It should be noted though that it is always best to treat secondary infections; one does not ignore them and they can be more problematic than the original disease process.
4. It is also possible that the real cause is a combination of infective organisms, such as viral and bacterial. If such were true, it is possible that antivirals might be needed. It is also possible that these co pathogens would not be an issue in most patients and as their immune system recovers they would be completely cleared of such secondary infections, while some other patients with more advanced secondary infections might need antivirals as well to get a complete cure. These copathogens are known to be present in CPn infection but it is not known for certain when they might need to be addressed and when they can be ignored.
5. In the lab it is possible for CPn infected mice to develop secondary autoimmune disease through epitope spreading. In other words, the body attacks the CPn but in its effort to clear the infection it also accidentally makes antibodies that are self-reactive. It is possible that CPn causes MS but that a secondary autoimmune process is also in play. If such were true, it is possible ridding the person of the infection and addressing the autoimmunity as well would best facilitate treatment. On the other hand, rheumatic fever, which is an autoimmune disease secondary to a germ (strep), is self-limiting once the germ is gone so even if CPn autoimmunity were an issue it may not be something that needs treatment.
I have been told by my neurologist that only about 10% of people with MS actually have myelini active antibodies in their blood that can be treated with the new treatment in development in which they filter your blood and extract the myelin active antibodies, radiate them, and reinject them as a vaccine so your body destroys those antibodies (this treatment is called "Tovaxin"). Is it possible that 10% of people infected with CPn develop autoimmunity? Such things are unknown, but certainly could complicate the picture and the eventual "best" treatment.
The actual facts of how MS develops and what co factors are in play is unknown. The theory that CPn causes MS is plausible and very compelling, but it is possible some of these other co factors will be understood as more people are treated this way or as more research comes out.
Treating Empirically has some limitations also.
1. There is no reliable test for cryptic infection. However, empirical treatment is problematic because it may be hard to know when you have enough objective improvement to know it is working for you. In terms of MS, some of your symptoms may be caused by axonal degeneration and permanent scarring which may not go away without regeneration of some kind; it is hard to know what "I still have a weak leg" means in relation to CAPs treatment. It may be that some people with disease of shorter duration recover function with EDSS scores lowering, while others with more longstanding disability may "only" stop progressing. However it should be noted that the brain is much more plastic than used to be thought and it is likely some level of regeneration is possible if the disease process is stopped (just as people who've had strokes can recover more function with aggressive rehabilitation than anyone ever thought before recent research proved it was possible). If you do not have noticeable or dramatic exacerbations it might also be some time before you know you have stopped progressing, or if you have stopped. This can be devilishly frustrating.
2. It is possible that reactions to the antibiotics do not mean that a CPn brain infection is present. There could be other bugs, even normal intestinal bacteria, causing some systemic reaction to antibiotics. It is also possible that you are reacting to CPn in your body, but none of it has passed through the blood brain barrier and thus none is in your brain. If this were so, one could "react" to antibiotic treatment but the real MS process would go on unhindered.
3. It is also possible that the antibiotics themselves ameliorate the disease process in a way not related to their antibiotic activity. There is a fair amount of reserch on minocin, a tetracycline antibiotic closely related to doxycycline, which suggests it helps MS by altering the immune system and dampening it a little thus reducing lesion loads and exacerbations. If you are a person who believes the CPn model, you might see that relief as an antibiotic effect instead of any immune system modulation. However, one cannot determine cause by results so such positive outcomes do not prove either theory.
4. It is possible the adjuncts to treatment, the supplementsi, have an ameliorating effect on symptoms all by themselves. Many people who start the adjuncts first report that they already feel better before they have begun taking antibiotics. It is possible that a combination of supplements and amelioration of symptoms by the anti-inflammatory effects of antibiotics combine to create some apparent improvement independent of any antibacterial activity.
5. The protocols here are based on current research and are still evolving as new material comes out. Even if the MS/CPn model is proven it is possible the eventual protocol will include elements not now known, or that co factors will be understood and addressed in a way not now imagined.
What IS a "proven" approach?
If a person is given a pill filled with sugar, a placebo, and believes it will help, about 35% of the time it will actually help them. Their belief activates their healing in some way we do not thoroughly understand. It is more than just "thinking" they are doing better-- they really do better.
The CRAB drugs are all considered "proven" meaning that they have been given in blinded trials to larger groups of MS patients and shown to be marginally better than placebo. For more on this and why I used the word "marginal", please look at the objective Cochrane reviews of these drugs on Pubmed.
MS is a disease of unknown origin. It is often stated as being autoimmune, but that is actually an unproven theory. For autoimmiunity to be proven, it would need to be shown that a specific part of the immune system is different consistently in MS patients and that inducing this precise difference in other animals, preferably primates, results in a relapsing remitting neurodegenerative disease that eventually becomes progressive identical to MS. After decades of looking, no such trigger has been uncovered.
In light of the unknown trigger for MS what drug manufacturers can do for us now is to treat based on the generally accepted "best" theory for MS, do a trial, and see if they actually get any positive results with their drug. These trials result in "proven" therapies even though the cause of MS is still unknown: they do not prove the theory that MS is autoimmune, they only show that the approach used helps in some unknown way. These are relatively expensive trials and are undertaken for promising therapies likely to recover the cost of the trial. This is just a simple business reality, not a conspiracy.
It is extremely unlikely that CAPs will be trialed in the way described above to see if it helps patients with MS. The drugs are long off patent so they cannot generate the profits necessary to make it possible to recoup the expense.
Our best hope is for someone in academic research to look for and find CPn in MS lesions by preserving a donated MS brain properly and staining the samples near lesions correctly to see inclusions. This would result in a proven association with MS. However, even if such were discovered tomorrow it would likely be a long time before there was a universally accepted and proven antibiotic regimen for patients (although IMHOi the VU protocol is the most likely due to the extensive research they have done).
As an illustrative example, it has been known for years that atherosclerotic lesions have CPn in them, yet the medical literature continues to debate whether or not it is a secondary infection or causative, whether or not intermittent mono therapy antibiotics reduce second heart attacks, whether it has triggered a secondary autoimmune attack on the blood vessels, and whether it is even possible to get rid of cryptic CPn infections. I have not yet seen anything remotely resembling a CAPs protocol being tested on atherosclerosis patients. During these years of debate on the issue, dozens of patent medicines to treat cholesterol have come out and patients needing some kind of treatment today are offered these new drugs because nothing related to CPn and atherosclerosis is proven. During these years also heart disease remains the leading cause of death. Once again we see drugs go to trials based on the most generally accepted theory, in this case that cholesterol causes atherosclerosis. This offers proprietary targets (cholesterol is a viable target for drugs) and when the created patented drug works better than placebo in reducing cholesterol, the drug is approved for use in patients. However, if CPn causes atherosclerosis, there will never be a cure by reducing cholesterol.
With a few exceptions, science moves very slowly with a lot of back and forth research before final conclusions are drawn and everyone agrees on one fact as a generally accepted principle to guide treatment. This process is greatly enhanced when a commercially viable product is the agent in question, and there is not one for CPn.
No one can or should make any promises to you about how you will do on CAPs, there are unknowns as described in this page. What I can tell you is that some people, though not all, have had verified reductions in EDSS scores using this approach and that if CPn causes MS then this is the best hope you have for a cure.
With all these limitations duly noted, there are good reasons to initiate a CAP for Cpni despite these scientific uncertainties. In many cases there are really no good approved treatments for the individual person. Additionally, CAP protocols do not conflict with other approved treatments so it is certainly possible to do both. CAPs are also low risk and low cost, and if you are a person who engaged in Empirical treatment and reacted to the NACi, the antibiotics, or the protocol in general you know you are dealing with some kind of bacterial load, the eradication of which cannot help but improve your system.
Addendum: In a thread started to discuss this Limitations page found HERE Dr aWheldon made a comment on this page that lends adds more food for thought and I have pasted it below. The link to the thread is worthwhile reading also.
Dr Wheldons's comment on this page:
I always look forward to Marie's posts; this one is an analysis of the limitations in the viewpoint that C. pneumoniae has a role in Multiple Sclerosis. It is impartial and thorough. I read it carefully and with great interest, and recommend others to read it also.
As I read it I found myself pondering the manner in which medicine is practised. It is often not very rational. I recall, as a medical student, standing in a women's ward in a big mental hospital which had been built in the 30's in beautiful countryside. It was a consultant ward round; we had almost finished. We came to one very perplexing woman who was behaving very bizarrely. Her symptoms fitted no psychiatric stereotype. The consultant clearly didn't know what to do. Two psychiatric social workers were having a private but rather loud discussion about tatting in the background. The sister was keeping her thoughts to herself. The registrar was quietly doing isometric exercises. 'Tell you what,' said the registrar, suddenly, and rather impertinently. The consultant looked at him. 'Have you a suggestion?' he asked. 'Yes,' said the registrar, smilingly. 'Let's give ECT[1] a whirl.'
I've never forgotten that phrase: 'let's give ECT a whirl.' Give it a whirl! What an odd way to recommend a much-argued treatment, and yet how refreshingly honest! There is a deadly comicality about it. The main thing about recommending something on a hunch is never to forget that it is on a hunch. When Sarah was falling through the EDSS numbers, the diagnosis made, the Internet searched, the original Vanderbilt paper discovered, the objections by Hammerschlag discovered also, I must confess that I didn't weigh all the evidence scientifically. I did a brief risk analysis (aggressive SPMSi: deadly - doxycycline: one of the most harmless antibiotics available) and started. It was a hunch that maybe the Vanderbilt workers were right and that the entire neurological Home Fleet was wrong. (This was in 2003.) I remember reading an interview with Hammerschlag in which she said ". . . this study shows that it's much too soon to put MS patients on antibiotics for Chlamydia pneumoniae." And as I read these uninspired words that risk analysis went through my head. Other people's risk analyses came to mind, too: the risk that if MS has an infective input (as seems likely from the epidemiological data, even if one does not stipulate a pathogen) the administration of a T-cell immobilizing antibody may be clinically rather unwise. Hippocrates was surely right when he said: 'first, do no harm.' Many times, as a doctor, I have to make recommendations on poor or inadequate information. One has to admit to making assumptions. Often one can only say, 'If I were in your place I would take this road.'
So Marie is quite right: there is a weight of evidence on either side of the equation, and it's wise that we admit this, even if positive evidence carries more weight than negative evidence. We are still in the opening pages of the story. But I have a hunch that in 20 years' time the idea that C. pneumoniae infection is a key factor in the multifactorial illness MS will be mainstream.
[1]ECT - Electro-convulsive Therapy.
-D W