A new concept for MS and other autoimmune diseases

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Scott1
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Re: A new concept and treatment options for MS

Post by Scott1 » Thu Jan 08, 2015 2:30 pm

Hi Leo,

I stumbled on something that was on a thread some time ago and thought it may be of use to you. There was some work done by Chinese investigators into the Lactoferrin as an inhibitor of EBV. The study is here - http://www.karger.com/Article/Pdf/336178 and the old thread is here - http://www.thisisms.com/forum/general-d ... 24261.html .
I was intrigued by the concept so I became the lab rat. It did no harm but I had a terrible feeling of impending doom and nervousness while I tried it out. As soon as I stopped the emotional impact ceased. It was very dose related and I don't know why I reacted that way. The side effect is my extremely unpredictable bowel became normal and has stayed that way.
As I discussed elsewhere I really believe I triggered my last attack so experiments are not always for the good. None the less, I should point this article out to you in case you might recognize a connection that could help you.
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Re: A new concept and treatment options for MS

Post by Anonymoose » Fri Jan 09, 2015 7:59 am

Barge. Hey guys. I googled lactoferrin and candida (my current obsession) and found a load of stuff. It's pretty well summarized here. http://www.thecandidadiet.com/forum/yaf ... errin.aspx

Maybe you (Scott1) were working on candida instead of or in addition to ebv. That would explain the lasting gut health improvement....

I also wonder if Wahl's success wasn't necessarily a pure diet/nutrition thing. Maybe she knocked down ebv overload with chemo and antivirals and later cleaned up the rest of her mess by reducing the candida with her very anti-candida diet.

Maybe I'll dig up my old lactoferrin and give it a try. I'm having a hard time getting any more die off with any of the anti-candida things I am willing to take now.

Scott1, any theories about how you may have brought your relapse on? Mine were so long ago I only know they were seasonal but now I'm wondering if that wasn't because of seasonal diet changes and candida load. The first year I skipped my seasonal relapse I was drinking tons of Ceylon cinnamon tea which as it turns out is anti-candida. Just thinking...

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Re: A new concept and treatment options for MS

Post by Scott1 » Fri Jan 09, 2015 2:08 pm

Maybe go to my posts from Sept 13th 2014 to save Leos thread http://www.thisisms.com/forum/regimens- ... 19-30.html

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Re: A new concept and treatment options for MS

Post by Leonard » Thu Jan 15, 2015 1:49 am

Hi Scott,

just found this on TIMS: http://www.ncbi.nlm.nih.gov/pubmed/25580822 on Proteomics of a conundrum: thoughts on addressing the aetiology vs. progression of Multiple Sclerosis.
things seem to be moving in the right direction...
do you know these people?

despite their turn on things, the oligodendrocyte degeneration is still somewhere down the cascade of events.
but being in a department of molecular physiology, at least these people seem to be well placed.
as said before, solving MS requires a multidisciplinary effort.

summarising from the above, it seems the cellular fat metabolism is central and in particular the Omega 3/6 ratio and the saturated fat contents.
the balance is critical for cellular homeostasis and normal development.

with too much LA-AA conversion, ALA-EPA/DHA conversion is inhibited (they compete for spot, same enzymatic pathways for conversion) and cells are predisposed to excessive inflammation.
saturated fats then cause platelet aggregation and reduce anti-inflammatory properties of HDL which impairs (sub)endothelial function.
I have suffered from hypertriglyceridemia for most of my life which is a pivotal step in artherosclerosis (and which -incidently and as you might expect- can be treated by Omega 3).
inevitably, the virus may have been involved already at an early stage.

with a compromised (sub)endothelium, binding of EBV to human PMN (cell priming) results in an increased release of AA when stimulated.
this will cause the ratio Omega 3 to Omega 6 to get out of balance even further, where research suggests that in particular the relative lack of Omega 3 causes the inflammation.
I believe both excess AA and lack of ALA will then be mediating in the signalling pathways that turn on the immune response (which is then followed on by a rushing in of white blood cells).
over time, the invasion and accumulation of white blood cells will turn the atherosclerosis/wall thickening into an endothelial dysfunction http://www.ncbi.nlm.nih.gov/pubmed/24416810.

you may be able to reduce the (oxidative) LDL and increase HDL a bit by diet and by Simvastatin/Niacin and Metformin.
but apart from manipulating a bit the fat metabolism, I would be extremely cautious with Lactoferrin or any other EBV inhibitors.
I don't know what to think about chemo (see next postings on chemo).
my bad experience with valacyclovir has learned me an important lesson: that is that the short-term response of the virus is critical.
I think valacyclovir reactivates the virus (in my case spots in the groin re-occured) with unpredictable effects.

Leo
Last edited by Leonard on Thu Jan 15, 2015 6:42 am, edited 8 times in total.

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Re: A new concept and treatment options for MS

Post by Leonard » Thu Jan 15, 2015 2:26 am

Anonymoose wrote: I also wonder if Wahl's success wasn't necessarily a pure diet/nutrition thing. Maybe she knocked down ebv overload with chemo and antivirals and later cleaned up the rest of her mess by reducing the candida with her very anti-candida diet.
you are right, this has crossed my mind as well. I recall the wife of Mitt Romney who has MS, was apparently in a good shape when I saw her on television, and also gets chemo. I suppose with the effect that it knocks down the virus...
and "the cleaning up of the rest of her mess" may include a strengthening of the gut-related immune function through the diet, to keep the virus down.

what the heck is going on here? should we all get chemo to get rid of the virus?
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Re: A new concept and treatment options for MS

Post by Scott1 » Thu Jan 15, 2015 3:18 am

Hi Leo.

I don't know them but I don't disagree with the point they make. They're not the first to question the dominant model.
I've also wondered about chemo. It's so broad, it would better if it was targeted. Often you read of some success with stem cells but they never highlight the chemo beforehand.
On the general topic of fats, it would help if we hand a better grip on how electrons are transported and why they move from molecule to molecule. Ultimately its the rules they follow that determine how everything interacts. It means we have to go level deeper but I'm sure we would have a better understanding of how interactions occur (or which ones cant be right).

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Re: A new concept and treatment options for MS

Post by Leonard » Thu Jan 15, 2015 6:56 am

it seems there are two problems: that is the cellular fat metabolism and that is the virus.
tacking the disease through the fat metabolism is a long way but may be worth going (as George Jelinek and Swank's patients have shown).
for tackling the virus in MS (probably closer to the causal factor and perhaps faster), is this a candidate for chemo? http://www.ncbi.nlm.nih.gov/pubmed/23692048
it is not the first time we come across rituximab, apparently the viral count is down and inflammation diminishes.
would be interesting to know what other MS patients have used as regards chemo.

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Re: A new concept and treatment options for MS

Post by Kronk » Thu Jan 15, 2015 12:39 pm

Scott1 wrote:I've also wondered about chemo. It's so broad, it would better if it was targeted. Often you read of some success with stem cells but they never highlight the chemo beforehand.
Couldn’t agree more!

There are many different types of chemicals used in Chemo. They are specifically designed to combat different types of cancers. All chemos affect other parts of the human system as they are all poisons. However, they typically have a very short life in vivo before the body eliminates them. So only the fastest replicating cells are seriously impacted such as cancer cells, hair cells, and immune cells. Theoretically a chemo agent could be designed to attack a specific cell, but one would need to know what that specific cell is…

I am reminded of this story, it is older and I am sure there have been more successes since. The treatment consists of a high dose of chemo followed by stem cells. It is basically a total re-write of a persons immune system. MS may not start in the realm of auto-immunity but thats where the damage appears to come from. If you erase the immune system you may be taking the gun out of the virus's hand. Whether the virus will eventually influence immune cells again in future is a possibility, but due to the fact both identical twins may not contract MS, I think the chances are rare.

http://www.cbc.ca/news/canada/ottawa/ot ... -1.1368173

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Re: A new concept and treatment options for MS

Post by Scott1 » Thu Jan 15, 2015 12:45 pm

Then Anonymoose is the one to talk to.

The "mab" at the end of the drugs name stands for monoclonal antibody so its aim is to bind to only one end of the "V" on a "Y" shaped target. Problems arise if it binds to the wrong thing so the procedure should be done by people who know what to look for. Monoclonal antibodies are clearly a solution but you really want to know how it works.
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Re: A new concept and treatment options for MS

Post by Anonymoose » Thu Jan 15, 2015 4:43 pm

Burning ears...

I think, given the history of rituxan for ms, it is a guaranteed win so long as you ensure CNS penetration. The effects may not last forever but you will at least give ms a good kick in the teeth. Add valtrex to hit lytic ebv as fewer immortalized B cells (which will come back if you don't address lytic phase) would hopefully lead to fewer self antibodies...doesn't matter if ebv is the cause or not...ebv could only serve to make things worse. Also, before you do the rituxan/valtrex, make sure you are clear of any other obscure health issues...like my candida issue to which I was completely oblivious. I'm pretty sure a candida overload is what caused my post-rituxan difficulties...my ms was better from the start and still is but other issues came up. Hopefully I'll see some changes in my queer lab values after 6 months of candida treatment.

LR1234 has a doc who tests her B cell levels and what not so you could probably get better data from her experience. She's doing great after her rituxan round last year.

I wish they'd go ahead and approve rituxan for ms. It's ridiculous that it hasn't been yet!!

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Re: A new concept and treatment options for MS

Post by CarpeDiem2015 » Mon Jan 19, 2015 12:12 am

Hi,

I'm relatively new to this forum, and am trying to find my way around with respect to what might work for PPMS. Does / Could the treatment being discussed in this thread pertain to all MS sub-types including PPMS?

Thanks,
Paul

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Re: A new concept and treatment options for MS

Post by Leonard » Mon Jan 19, 2015 2:45 am

The answer is yes. PPMS is the only real form of MS. The relapsing remitting MS where the medical profession has concentrated on for so many years is only secondary and pertains just to the early signs of a body fighting the virus.

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Re: A new concept and treatment options for MS

Post by Leonard » Tue Jan 20, 2015 1:16 am

I have revised the thesis taking into account the comments made in the last few pages. The sections in blue are new and add substantially to the theory. Any comments would be welcome.

A new vision on autoimmunity – towards a revolution in healthcare

I am an MS patient who was trained in a technical discipline. But when I was diagnosed with MS in 2004, I became extremely motivated to unravel the disease that increasingly ruled my life and started to learn more about the disease. In the meanwhile, with my own experiences as an MS patient in mind and with the help of the vast amount of medical literature available on the Internet, some professional advice and the social and patient fora, I have become a semi-literate. The journey has led me to a new understanding of the disease that is presented here.
Hundreds of links to publications in the medical literature can be found in the postings in this thread.

Paradigm changes often come unexpected and from the outside, and are motivated either by young people who are new to the field or by people who look with fresh eyes at the problem. This has definitely helped me because I did not have to unlearn, my mind was not set by old dogmatic believes that every medical student has to learn if he wants to pass his exams, and I could see new connections and concepts that others perhaps could not see, believe, accept or propose.

A critical need to open the mind set

Autoimmune diseases like Crohn’s Disease and Multiple Sclerosis (MS), in which the immune system attacks its own body rather than predatory invaders, affect 5-20% of the global community. The current scourge of immune diseases points to a growing problem of an overall weakening society. [more on scope of problem, statistics, hits ever younger people] If the trend is not changed, consequences for the general health of our population and that of future generations may be far reaching.

We must spot current trends in societal health, take these trends extremely serious and investigate what is driving them as a matter of urgency. To this end, we should question the status-quo on autoimmunity.

However, as the weight of the status-quo is so immense, every change proposal is at risk to collapse under that weight. Significant systemic problems are pervasive and hamper a course towards investigating or even considering alternative views. The risk is a stagnation while the debate does not get a fair chance and may be dead even before it has started.

In order to find a way out of the impasse, it will be critically necessary that the matter is approached with an open mind, and that alternative views on autoimmunity are explored and new connections investigated with urgency and with force.

The viral connection

The current scourge of immune diseases is explained by an immune system that gets ever weaker. There is a multitude of underlying factors: an unhealthy diet (the ratio of Omega 3 to Omega 6 and satured fats drastically changed from 1:1 to 1:16, we forgot about fish on Fridays, the balance of fatty acid intake is important for homeostasis and normal development, the emergence of inflammatory diseases correlates to the evolutionary aspects of our diet), poor quality food (e.g. engrainisation, ‘hardened’ wheat, soil depletion, a lack of flavonoids which generate antioxidants, hydroponic plant growth, lack of earthing), a lack of immune system training (e.g. extreme hygiene and indoor/office life, we forgot about fasting which is deep in the Old Testament, people who work outdoors are generally much healthier - earthing), and stress in a very broad sense. The immune system also weakens with age.

When the immune system weakens, the herpes virus emerges [herpes is a family of viruses]. Most of the human population have it and it has been with us for millions of years, even when we were still apes hanging in the trees of Africa. But all the time it was kept in control by a good functioning immune system. However, the last 50 years, something new is happening that has not been seen before in the history of mankind [on a smaller scale: Sumeria (overfarming) and the black death (people in upper class of society were more immune because of diet)]. Our living conditions have changed so profoundly that the immune system does not keep the virus in check anymore.

The world of the herpes virus and the endothelium

The immune system and the virus have evolved alongside, for millions of years. The fact that cytomegalovirus-like viruses are found in very many species – including in fish - suggests that it evolved along side with us for a very long time and adjusted itself entirely on man. In fact, humans and the virus keep each other in balance and where the virus helped along the long, joint road through attack and defense to build up our present immune system.

The virus nests in the vessel wall, and occasional breaks out and causes major changes in the immune system by the formation of highly aggressive effector T-cells (CD4 + and CD8 +). This type of immune cells depends for their survival on the presence of the herpes virus and comes in healthy people only when they are infected with the virus which itself is no longer detectable.

The relationship between the well detectable CD4 + and the CD8 + T cells and the virus means that the virus itself is somewhere in the body, tucked deep inside the endothelium. The virus itself is no longer detectable in the blood. An eminent immunologist once told me that the virus infection itself is removed from the blood within a day. But the virus tucked deep inside the subendothelium leads to a low-level chronic EBV infection.

The virus and the fat metabolism

As our immune system weakens and the virus emerges deep in our endothelium, preincubation of the cells with EBV primes the cells (EBV infected polymorphonuclear leucocytes) and when stimulated start a response that leads to the release of pro-inflammatory lipid mediators (arachidonic acid or AA). The AA which is inflammatory (oxidative LDL relates) outcompetes in the enzymatic conversion pathway ApoA1 which is anti-inflammatory (HDL is directly related). Omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis. Slowly, the ratio Omega-3 to Omega-6 changes because of AA release and the ApoA1 level is reduced (25% in RR, 50% is SP and 75% in PP). And inflammation starts.

The EBV infected B cell is a prolific producer of superoxide and over time we produce excess peroxynitrite. Although the peroxynitrite may inhibit viral replication, it disables glyceralderhyde 3 phosphate which impacts the sodium/potassium pump and cell viability. It is a system that feeds on itself: The imbalance of the ratio of ATP to ADP to AMP causes the cell to shed AMP which further lowers ATP, the fall in adenosine lowers purine levels and uric acid falls so we lose a potent scavenger of peroxynitrite.

Over time the vitality of the cell declines as ATP levels decline and the loss of some AMP leads to a fall in Adenosine (endogenous inhibitor of arachidonic acid) and, in time, a loss of purine from Adenosine loss. Ultimately energy levels decline and uric acid levels fall. The loss of Adenosine will lower the ability to control inflammation. And the endothelium inflammates.

A cascade of events follows: further immune cells, more superoxide, more peroxynitite. These are very localised processes, short lived with restricted diffusion but still go across cell membranes. This leads to an initiation of a lipid peroxidation processes from which the demyelinating plaques and the lesions follow. The invasion and accumulation of white blood cells will turn the atherosclerosis/wall thickening into an endothelial dysfunction. As such, the damaged endothelium initiates many pathological process and plays a key role in MS.


The viral tolerance theory – the typical demyelinating MS plaques explained

During periods that people are immune compromised (can be the fetal period, the period of the newborn and immune deficient periods), the virus can incorporate some of its genes in the DNA of permissible cells. As such, the virus itself is not programmed to reactivate at specific time intervals but it is the immune system that weakens.

The gene transduction occurs during immune deficiency periods. The incorporated viral genes (transgenes) are tolerant to the body or no immune memory against these transgenes has established.

In MS, in particular the oligodendrocyte precursor cells (OPCs) will be infected. These oligodendrocytic stem cells and their progenitors are preferred by the virus because they differentiate and help replicate the virus. Also for that reason the bone marrow will be infected. Chronic cerebro spinal vascular insufficiency (CCSVI or narrowed internal jugular veins) is a factor – most probably a birth defect - that broke the BBB tissue in an earlier phase. [in rheuma arthritis it is the cartilage of the joints, in MS infection of the cartilage of the sinuses is an issue that helps spreading the virus, for Crohn’s disease permissible cells are in the intestine]

People with transgenes in their body are healthy but predisposed to develop a disease. Predisposed people become diseased when they are infected with a microbe that shares epitodes with the transgenes present in the transgenic cells and will cause an immunological reaction. A chronic low-level EBV infection is suspect in MS but also a Hepatitis vaccinations has been suggested as a trigger. Crohn's disease is associated with measles.

In MS, specific T- and B-cells will pass the CNS and cross-react with the transgenes in the OPCs. Due to this cross-reaction, many OPCs will die which leads to a diminishing number of OPCs, of dendrocytes and a reduced myelination of neurons. EBV resides in the B cell and immortalizes it. So in reaction, the immune system produces more and more. [The count of EBV/Herpes immune cells in my circulation is very high, about 20 x max.]

During this cross-reaction, many mediators will be released by the infiltrating T-cells. This will increase angiogenesis and cause hyperproliferation of surrounding tissue cells in the CNS which in turn causes the pathological lesions (sclerotic plaques) typical for MS.
The symptoms of MS will be mild in relapse-remitting MS but severe in progressive MS depending on the kind of virus that has incorporated part of its genome in the oligodendrocytic stem cells. Inflammatory viruses such as VZV will be associated with mild diseases whereas onco viruses such as EBV will be associated with progressive MS. [I do not exclude the possibility that the VZV mechanism (microbleedings, angiopathy, acute inflammation by blocking of receptors) is followed later on by the EBV mechanism (immortalized B-cells, autoimmunity of transgenic cells) where precisely the kick-in of this latter mechanism explains the second peak in the graph of age of onset of MS. ]

The biochemical reaction hypothesis – the fatigue explained

Besides the immune reaction against the OPCs, the high load of immune complexes has a second important effect. This is all about fatigue, deterioration of the cell machinery and cellular respiration, disabling glycaldehyde-3 phosphate, the peroxydisation of lipids and other disturbances crucial to the progression of MS but not necessarily major demyelination.

The immune cells have substantial super-oxygen generating capability. The superoxide reacts with the nitric oxide and forms peroxynitrate. The peroxynitrite is by far the worst free radical which causes huge oxidative stress, immune response, jams the gates/mitochondria of the cells, causes effects on the mitochondrial electron transport chain, electron pump inactivation, inhibits ADP to ATP conversion and depletes energy in the form of ATP. And it poisons fat tissue and causes lesions where the brains, biologically seen, are just a lump of fat. I think it also causes what is called herpetic neuralgia where fibromyalgia is not far away.

The lack of energy in MS and other lesions is thus a co-morbidity factor caused by the VZV angiopathy in combination with the EBV high immune complexes. As the number of active gates goes down, we see an increasingly big temperature effect in patients with MS and a loss of muscle strength and sensitivity in the periphery which is an effect possibly as important as the disconnect in the brains. And as cells shrink in size because gates/mitochondria fail, it causes whole brain atrophy. Hence, the typical fatigue, weakening of muscles and whole-brain atrophy observed in MS patients is partly caused by the chronic VZV/EBV infection but with a completely different underlying mechanism than the demyelinating plaques in the brains.

[an extensive analysis of my blood revealed that there are only a few parameters out of their normal margin: that is the high concentration of herpes/EBV immune complexes and high titers of muscles, hence I am eating my own muscles and with that also the connection between nerves and muscles]

In parallel to the MS plaques and immune cell activation in the brain, the NF-KB is triggered by the biochemical cycle mechanism, causing elevated cytokines that contribute to raising the inflammation and Th activity. Where, at some point, mechanisms become all convolved.

A general dysregulation of the metabolism – interlocking vicious cycles

The virus is causal and leads to a general dysregulation of the metabolism.

The problem of disease progression can not be solved by metabolic factors. For sure, hormones are an influence. Hormonal deficiencies often relate to symptoms belonging to lupus, CFS or fibromyalgia or other auto immune diseases. [In my case some hormones were on the low end including cortisol and – as a derived product - testosterone]

At some point in the autoimmune disease process, the HPA axis will be affected causing hormonal deficiencies starting with cortisol. This will have its effects on the gut and further weaken the immune system, thus causing a vicious cycle. [to note: gut problems often precede an MS diagnosis; 90% of the immune system resides in the gut; the role of bacteria in the gut which may help solve autoimmune diseases such as e.g. diabetes T2, the central role of the gastro intestinal tract for good immunity]

While hormones are an influence, administration with hormones (e.g. cortical and DHEA) won’t be convincing. Without tackling the virus and the viral infection, the problem will persist.

This is also true for infection by bacteria and fungi including Borrelia and Cpn, toxoplasmose and such things as toe nail fungus [Candida infection] which get their chance when the immune system is fighting the virus [IgG3 depletion]. The infection will aggravate the situation and challenge the immune system further. It is important to get rid of all bacterial infections but fighting the infections alone won’t be enough.
Besides the endocrinological disorders and infectious diseases, there is yet another loop, from the psychological to the physiological. (Short term) stressors that initiate cases of multisystem illnesses act by stimulating nitric oxide synthase (NOS) activity and consequently produce increased levels of nitric oxide and its oxidant product peroxynitrite. Initiation is converted into a chronic illness and a lowered energy metabolism through the activation of vicious cycle mechanisms through which chronic elevation of nitric oxide and peroxynitrite is produced and maintained. All three nitric oxide synthases have been shown to be involved (eNOS, nNOS and iNOS).

The NF-KB is triggered by the biochemical cycle mechanism. The increased NF-KB activity will lead to increased iNOS activity by stimulating through the inflammatory cytokines IL's, TFN and IFN the activity of the iNOS gene itself.

There is a combination of stability and instability, positive and negative feed back loops, leading to what is essentially inflammatory biochemistry. [vicious cycle is the NO/OHNOO hypothesis – Martin Pall]

MS is therefore a subtle multi factorial disease where a number mechanisms and vicious loops are convolved. This explains the erratic course of the disease, and the large variety of symptoms and disease progression seen in MS patients.

Towards to a new paradigm for autoimmune diseases

In our current system for medicare, we see a very large number of overlapping autoimmune diseases with different names. Every expression of a neurological set of symptoms got its own name, based on several types of observations. And we see various signs and symptoms that are overlapping e.g.: slowly progressive symmetric distal sensor motor neuropathy, muscle loss, difficult urine retention, pain worse at night, gender bias, fatigue, distorted Ca levels and inactivated pump mechanisms.

But in fact, a bigger common scheme is underlying. A scheme that encompasses the wide variety of observations, their patterns of case initiation, their chronic nature and many of their shared and unique symptoms and signs of the chronic phase of the disease. A scheme that explains many unexplained observations and the multiple similarities of these illnesses by a simple conceptual framework.

We need to develop and accept a new paradigm based on the understanding of a viral cause of autoimmunity and indeed MS. Traditional major disease paradigms should be complemented by a new model based on virology and biochemistry.

A highly disruptive course by anti-viral treatment of MS

With the viral causation of autoimmunity, treatment of the disease by anti-viral medication should be a first choice. In fact, the statistics of MS patients that attract HIV and start anti-HIV treatment are very convincing where, a few years after starting with the treatment, the MS just dissolves providing an indication for the fabulous self-regenerating capacity of the human body if the causal factor is removed. Also the results of chemo therapy to kick down the virus look very promising.
Last edited by Leonard on Tue Jan 20, 2015 11:59 pm, edited 1 time in total.

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Re: A new concept and treatment options for MS

Post by Scott1 » Tue Jan 20, 2015 2:36 am

Hi Leo,

That is the best, most logical explanation to date.

Regards

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Re: A new concept and treatment options for MS

Post by Leonard » Mon Jan 26, 2015 2:09 am

This article on New Clues to Epstein-Barr virus mentions that EBV is associated with several types of cancer, including to (non) Hodgkin’s lymphoma and nasopharyngeal carcinoma. Now my grandfarther had the latter, a few years ago a cousin was diagnosed with the former. To me, this is an other sign of the EBV virus in the family tree, causing in my own case the MS.

http://www.sciencedaily.com/releases/20 ... 152738.htm
Last edited by Leonard on Mon Jan 26, 2015 8:09 am, edited 1 time in total.

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