Theoretical Immunology

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Leonard
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Re: A new concept and treatment options for MS

Post by Leonard »

I tend to see the Herpes virus is a constellation or a cluster of viruses, all of the same HERV family.

I think if you have a high load of EBV immune complexes, you are also likely to have a high load of other immune complexes such as Herpes simplex and Varicella Zoster. In my case, both EBV and Herpes simplex were about 20 times max. Varicella Zoster was not tested but I am sure that reading will be high as well. I remember red spots in the neck when shaving, before the MS diagnosis; this is a sign of Varicella Zoster.

The virus is with us for many millions of years, I tend to think the immune system is playing a cat and mouse game with the virus where its appearance may change over time. Where Herpes simplex is more inflammatory (in RR phase), Varicella Zoster may cause more permanent vasculopathy from microbleedings http://download.springer.com/static/pdf ... 9&ext=.pdf http://www.sciencedirect.com/science/ar ... 0X14000689 and EBV is earmarked as an onco virus. So the virus (or should I say viruses) work on different fronts using different mechanisms (as seen from within our current medical concepts).

Raltegravir is probably more effective than (val)acyclovir as the posting below suggests. I think that the case of the woman described here is not a-typical at all. http://omicsonline.org/evidence-that-ra ... ?aid=18477

I wonder whether we could or should combine the raltegravir therapy with rituximab (rituxan) http://en.wikipedia.org/wiki/Rituximab for a while (say few months) to keep the B-cells down and/or; with neuro muscular electric stimulation (see the above publication on Varicella Zoster which suggests "A newer potentially promising treatment for PHN is percutaneous peripheral nerve field stimulation" - remember Terry Wahls' success with NMES which was probably as important as her diet).

One possibility to get going quickly would be to sign a written consent for off-label use of Raltegravir at a standard dose of 400 mg twice a day. Any one any ideas?
Last edited by Leonard on Mon Aug 11, 2014 1:55 am, edited 2 times in total.
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Re: A new concept and treatment options for MS

Post by Scott1 »

Hi Leonard,

I know you are keen to go quickly but have you checked outside the obvious herpes viruses for other infections such I have suggested elsewhere. Please do investigate them. I am particularly concerned about JCV (see - http://en.wikipedia.org/wiki/JC_virus ). There can be problems with Rituximab. Go slowly, it's quicker in the end. Understand as much about what other infections you have collected along the way as you can.
If I was you I would get a doctor who will conduct the tests first. Rituxan is a monoclonal antibody. That means it should target just one receptor on the V of a Y shaped cell. This is something you don't want to go wrong. You can open yourself to unintended consequences if you don't prepare as careful as you can.
Try carrot juice, Q10 and L-Arginine, etc first. Then target other infections, then see what Valtrex does to you at that stage. After that try Rituximab if needed. You need to be really as clean and strong as possible first.
You've got the idea now prepare properly.

Regards
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Leonard
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Re: A new concept and treatment options for MS

Post by Leonard »

thank you Scott, much appreciated.
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Re: A new concept and treatment options for MS

Post by Leonard »

I think the Valtrex escapade raised inflammation, in particular in the bowel, including spots that appeared in the pubis/groin (Varicella Zoster Virus?) and a new episode of the Irritatable Bowel Syndrome.
I had seen these same spots just after diagnosis, now some 10 years ago but they disappeared after a while.
And the Irritatable Bowel Syndrome came back that had been with me already for many years before the diagnosis with MS.
This IBS disappeared, completely unexpectedly, when I followed a low fat diet (Swank) for half a year or so around 2008, and it stayed away.
And from experience, this period of low fat was the only episode in my entire "MS career" that my walking distance improved.
I gave up on Swank late 2008 which is probably the most stupied thing I ever did.

I had completely forgotten about all these things but now they came back, again completely unexpectedly.
This was not activated in the head; this is not brain – bowel, this is bowel – brain.
In this same context, I am beginning to believe that our stress (our poor stress handling) may also be caused by the oxidative stress, in other words, that the mechanism works in the other direction also here, that the tensed up shoulder is the result of the biological processes in the body.
And that it all starts in our biological center, that its very inception lies in our gut, and that our brains are in principle no more than a lump of fat. Of course, that lump of fat can do magical things when we listen to Beethoven's 9th Symphony, but biologically it remains in essence a lump of fat.
And that the link between brain and bowel has been grossly exagerated (with the HPA axis etc as secondary mechanisms but now you probably say this guy has turned completely nuts..)

I think now that the anti-viral medication may have triggered a re-activation of the virus, in the gut and the lower body, clearly with effects elsewhere where the virus and the immune complexes do their destructive work.
I had problems with balance, eyes, lower consciousness which fortunately all disappeared after a month; but disability progression continued, may have accelerated...
This is why the bacterial therapy recently reported here on TIMS may bring people back in remission, the bacteria are the enemy of the virus.
I also think that control over MS requires first and above all a resurrection of the immune system, and this is first and above all in the gut!
When I googled on gut immune system and satured fats, I found this article that may be central to MS and many other immune diseases: http://www.uchospitals.edu/news/2012/20 ... lkfat.html
Fermented foods may be critical too to help restore a healthy gut flora (look at the work of Natasha Campbell).

This Valtrex escapade and the above link also remind me of the story of my farther.
When he was around 65 years old, he was limping a bit with his right leg, had problems with his knee.
I can still see him come into the kitchen and seek support with his hands from the door or the wall; a bit like I am doing now (I am 58).
He never had MS, was diagnosed with diabetes 2, retired from his farm, started his diet (no sugar, no coockies..), Metformin..
His problems disappeared, dissolved, I guess without anyone being aware.
When he was 80 years old he walked fine, 10 kms or so.
At 83, after a period of severe stress, he had 3 attacks of what looked like Meniere.
Autoimmune behind the left ear, where I had a main stenosis.
He is now 87 years old, in good health where his diabetes 2 diet and in particular to refrain from coockies/bad fats (inevitably he did it for the sugar) must have preserved his health.
This reminds me of the British study posted here recently on bad fats.
[ http://www.scirp.org/journal/PaperInfor ... erID=28741 you find the full pdf by clicking just below the title]
I think we will see strong parallels of this study with the study under the above link.

In any event, for now I go back to the Swank diet as the only way to stop progression, I think for me it works.
And no coockies is part of that.
Also sauerkraut (fermented food) has a strong positive effect on my gut, I know this.
Recently an experienced dietist pointed me to the 4th generation supplements for the gut microbiota [Norgitan]; that may be a possibility too but when I took other gut microbiota supplements last time, they had an adverse effect..
I am ready to try anti-viral medication again (Valtrex, raltegravir/anti-HIV) under control of a good clinical trial.
And, with Scott, after other things/viruses have been excluded.
Last edited by Leonard on Mon Sep 01, 2014 1:33 am, edited 4 times in total.
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Re: A new concept and treatment options for MS

Post by Anonymoose »

Howdy Leonard,

Its like trying to untangle Christmas lights, isn't it?

Your ibs relapse has me wondering. Valtrex caused my calcitriol levels to go high which caused me pain. At least one person who experimented with calcitriol/vitamin d pulsing experienced bowel issues. Maybe the valtrex caused your calcitriol to go high as well? I know I've mentioned this before but at the time, I wasn't aware of the ibs situation.

Happy detangling :crazy:
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Re: A new concept and treatment options for MS

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Leonard wrote:I had seen these same spots just after diagnosis, now some 10 years ago but they disappeared after a while.
Whoa... 6 years before my diagnosis I noticed spots in my "area" enough to have me sufficiently freaked out to see a doctor who said it is NOT an STD. That was 6 years prior to Dx but when Dx i had numerous lesions.

On the fat issue I have always put a lot of faith in it. And while I know fermented foods are good for gut bacteria I am concerned about the level of Butyrate and its affect on EBV... The EBV lytic cycle is induced in cell culture by various stimuli, including sodium butyrate. Butyrate is a saturated short-chain fatty acid (SCFA) found primarily in cheese and other dairy products. It is also found in high quantities in Kombucha tea. While this tea has numerous other benefits being packed with anti-oxidants it definitely has high Butyrate as are many other fermented foods.

Interestingly another SCFA fatty acid ,which is not saturated, blocks the EBV reactivation actions of Butyrate. This is likely due to it using the same uptake pathways and enzymes. The fatty acid is Valproic and is used medically to treat patients with epilepsy and manic disorders occurring naturally in berries. Raspberries, Blueberries and Strawberries all possess high amounts of Valproic acid.

It is unknown how Butyrate promotes lytic activation and why it has differing effects on EBV reactivation than Valproic acid. I think this is due to the saturation of Butyrate and is yet another justification for the avoidance of Saturated fats. HOWEVER there are always 2 sides to any story and many claim a LACK of Butyrate is to blame for many inflammatory diseases particularly those in the bowel as it is the preferred fuel of the colonic epithelial cells. Perhaps we need to consume both in equal quantities? or find the balance that works for each individual?

http://huntgatherlove.com/content/human ... s-butyrate
"...Lower than normal levels of Butyrate have been found in patients with several diseases, notably types of colitis and inflammatory bowel disorder..."

http://fundedresearch.cancer.gov/ncipor ... sessionid= E378CCCEE6D2C7498E128C7D1BD2EA6F?action=abstract&grantNum=1F32CA165705-01A1&grantID=8391455&grtSCDC=FY%202012&absID=8391455&absSCDC=CURRENT
Effects of short-chain fatty acids on Epstein-Barr virus in B cell lymphoma
“…The EBV lytic cycle is induced in cell culture by various stimuli, including sodium butyrate. Butyrate is a short-chain fatty acid (SCFA)…”

http://www.ncbi.nlm.nih.gov/pubmed/15047835
"...Fatty acid synthase expression is induced by the Epstein-Barr virus immediate-early protein BRLF1 and is required for lytic viral gene expression..."

http://www.ncbi.nlm.nih.gov/pubmed/6257378
"...Effect of short-chain fatty acids on Epstein-Barr virus early and viral capsid antigen induction in P3HR-1 cells..."

http://link.springer.com/article/10.1007%2FBF01310678
"...Quantitative analysis of the Epstein-Barr virus-inducing properties of short-chain fatty acids present in the culture fluids of oral bacteria..."

http://wholefoodcatalog.info/nutrient/b ... ds/high/1/
Foods containing Butyrate
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Leonard
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Re: A new concept and treatment options for MS

Post by Leonard »

Further to my previous posting, I believe that strengthening the immune system is central to any therapy.

I believe that a healthy bacterial contents of the intestine will push the virus away and straighten the immune system.
Probably, my mass consumption of chocolate in the years before being diagnosed with MS - I guess it was to cranck up the metabolism - led to a devastating effect on the gut bacterial balance, the virus could replicate, block receptors and cause vascular damage. And I am not alone here, I know other MS patients with exactly that same excessive-eating experience.

Furthermore, I was vaccinated for Hepatitis and yellow fever in the years before MS diagnosis. I remember in particular the yellow fever vaccination caused terrible pains in the stomach/intestine. This wil not have been helpful either. This page suggest yellow fever is contraindicated for immune compromised people http://wwwnc.cdc.gov/travel/yellowbook/ ... -travelers

If you read on the first page, you will see that my grandfather had a nasal carcinoma. The therapy for this type of cancer is to strengthen the immune system. Now interestingly, the approach by Pender focuses on strengthening the immune system too but apparently is part of a much wider new treatment paradigm (for cancers and) EBV based on AdE1-LMPpoly-mediated expansion on T-cell polyfunctionality. whow..

http://cancerres.aacrjournals.org/conte ... 9.full.pdf

http://jvi.asm.org/content/83/12/6192.full (... and poorly recognized endogenously processed epitopes from virus-infected B cells.)
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Leonard
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The new thinking on MS

Post by Leonard »

I think that MS has many aetiologies. The Human Endogenous Retro Virus (HERV) of the W-family is central to the development of MS as well as many other immune diseases such as arthritis. Herpes simplex, Varicella Zoster (VZV) and Epstein-Barr (EBV) are members of the family. The chronic HERV infection is caused by a weakened immune system; and poor gut health and bacterial inbalance (which allows viruses and fungi to replicate or get out of control).

Chronic Cerebro Spinal Venous Insufficiency (CCSVI – blocked internal jugular veins) is specific to MS. CCSVI causes vascular damage (compromises the Blood Brain Barrier) as well as problems with the drainage/flow of the Cerebro Spinal Fluid (CSF). CCSVI links the drainage of the dural nerve system, the dural sinuses, and meningeal inflammation. It provides an explanation for meningeal inflammation and subpial cortical lesions exclusively observed in MS patients.

A third factor predisposing people is the kidney/renal system producing Asynchronous DiMethyl Arginine (ADMA), due to a late maturation of the system. ADMA is an endogenous inhibitor of all forms of Nitric Oxide synthase. The capacity to vasodilate is dependent on how much endothelial Nitric Oxide synthase we have to make Nitric Oxide. In people with MS there is a very high level of inducible Nitric Oxide synthase (iNOS) rather than endothelial (eNOS). The ADMA depletes eNOS and iNOS arises as a natural response.

In patients with MS, there is an unbridled production of EBV immune complexes in response to chronic HERV/EBV infection. These antibodies are non-working EBV infected B cells that release super oxygen. This super oxygen reacts with nitric oxide which is induced and available at high concentrations due to ADMA. The product is peroxynitrite which is by far the worst free radical nitrating the lipids (including brains). The peroxynitrite disables glyceraldehyde-3-phosphate and ADP/ATP conversion. This causes the lesions, jams the membranes/cells and causes a mitochondrial energy failure / the ion pump to fail.

The mechanisms causing disability progression and the lesions are only loosely coupled. The HERV VZV and EBV cause direct vasculopathy and inhibit OPC differentiation causing the replenishment of new dendrocytes to stall. In the RR phase, the virus causes inflammation by blocking receptors, the immune system removes the infectious agent and there is remittance (double peak in graph of age of onset suggests different mechanisms underlying RR and progrressive MS - herpes simplex is inflammatory virus, VZV causes microbleedings and disrupts the endothelial layer, EBV is onco virus).

Autoimmunity is explained by chronic high concentration EBV immune complexes cross-coupling with epitodes of EBV remnants in transgenic cells. About 8% of cells in our body is transgenic, after about 120 million years of evolution. The immune system is normally tolerant for transgenic cells formed during the first months of foetus.

A more detailed assessment of MS can be found on the 1st page of general-discussion-f1/topic15188.html
Last edited by Leonard on Tue Sep 02, 2014 12:15 am, edited 3 times in total.
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Leonard
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MS treatment options

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If there is only the slightest chance that there is some validity in the preceding analysis, I think the following treatment options should be further explored with urgency and with force, individually or in combination. The world and the problem are big enough for many 'competitive' trials.

directly tacking the virus:

- (Val)acyclovir
- Raltegravir (Isentress)
- Letermovir

From experience, I would hesitate to use valacyclovir as it reactivates the virus. Raltegravir worked for another patient who did not respond to Valacyclovir (you find a link in an above posting). Letermovir is quite new, is a very interesting development and seems to be a very potent drug against the cytomegalovirus
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807861/
http://www.bioportfolio.com/news/articl ... ntion.html
http://en.wikipedia.org/wiki/Cytomegalovirus

strengthening the immune system:

- Ade1-LMPpoly
- IgG3

The Ade1-LMP is the basis for what Pender does to get control over the HERV infection. I believe that strengthening the immune system is central to any therapy. This approach is perhaps more safe than the direct virus attack by medication.
IgG3 also helps the immune system, is normally depleted because our immune system is busy producing useless EBV infected B-cells. I know an endocrinologist who succesfully administers IgG3 to Chronic Fatigue Syndrome patients who share the high viral load.

strenghtening the gut bacterial content and therefore indirectly the immune system:

- Diet low fat / anti-oxidant phytonutrients / fermented foods (Swank/Wahls/Campbell)
- Gut bacterial therapy

We know about the diet. Thank you Kronk for your consideration on fat and viral replication. I don't exclude the Butyric acid issue brings us to the heart of the problem, and the Swank diet. I also think that I can see an overlap of the list of foods on http://wholefoodcatalog.info/nutrient/b ... ds/high/4/ with the considerations on http://www.uchospitals.edu/news/2012/20 ... lkfat.html wow..
Possibly gut bacterial therapy such as FMT, we know the story of Thomas Borody. I have tried FMT but for me this was not useful, possibly because the procedure followed in a local hospital was too simplictic. see e.g. http://www.thisisms.com/forum/general-d ... 20297.html

indirect support against VZV and in use for arthritis:

- Neuro Muscular Electric Stimulation

NMES is a potentially promising treatment for postherpetic neuralgia (PHN), the most common neurological complication of zoster. http://link.springer.com/article/10.100 ... 6-5#page-1
Nerve stimulation is also successfully used in Amsterdam as a therapy for arthritis.

limit damage

Rituxan and Vitamin D could also be mentioned as a scavenger of immune complexes and of free radicals respectively (to limit damage) and interferon to surpress the virus (Texas study).

not classified because I don't how or where

By synthesising proteins from the sheaths in a lab, and then injecting them into the blood stream at increasing doses, the body begins to learn that they are safe. The goal is to reinstate ‘self-tolerance’, where an individual's immune system ignores its own tissues while remaining fully armed to protect against infection.

http://www.telegraph.co.uk/health/healt ... ystem.html

Personally I am not sure whether this brings us closer to a solution. I see autoimmunity as a collateral damage of immune complexes cross coupling with common epitodes on cell walls. The virus and the immune complexes are the problem and I do not see how this therapy would change any of that.

And then of course there is the work of GeNeuro which developed the GNbAC1 monoclonal antibody that I do not know where or how to classify. In this context, it also occurs to me that there is the ex-ante and the ex-post. Directly tackling the virus aims to stop the cause, works before things have gone terribly wrong; work to do something with the envelop protein may aim to correct something when things have already gone terribly wrong...



It is regrettable that this line of thought is not found back on the agenda of ACTRIMS/ECTRIMS 2014 in Boston where about 10,000 neurologists and researchers gather. These conferences should be used as unique opportunities to launch new avenues of research and possible treatment but that seems not possible.

I have seen the same systemic problems and behaviour before in the telecoms world. This collective undertaking on MS has become an institutionalised bureaucracy, loaded with vested interest. That becomes stagnant. It risks to be leapfrogged by new initiatives, as happened in the telecoms world with the Internet. For the Internet (economic/competitive/growing from zero) that was all right and helped the new world forward but this domain is special as it is loaded with big moral and ethical issues.
Last edited by Leonard on Mon Sep 08, 2014 2:25 am, edited 5 times in total.
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Leonard
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Re: A new concept and treatment options for MS

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Viruses are known endothelial disrupters. In the case of MS, the endothelial disrupter is the cytomegalovirus.
http://en.wikipedia.org/wiki/Cytomegalovirus

This family of herpes viruses includes the Varicella Zoster virus (VZV). This small cohort study about VZV vasculopathy seems insignificant but in reality it is groundbreaking. The vasculopathy is not only for cerebral arteries but also for the finest capillaries, the 60,000 miles of blood vessels in the human body.
http://www.ncbi.nlm.nih.gov/pubmed/24556269
http://www.sciencedirect.com/science/ar ... 0X14000689

I think the cytomegalovirus / HERV lies at the centre of the endothelial disruption. Bacteria such as Cpn and fungi come into the picture in a different way. Because the immune system is producing EBV immune complexes that don't work it goes on and on and on, in an unbridled manner, to produce these immune complexes. And then the IgG3 is depleted (hypo gamma globulin) and the immune system forgets about the rest.

It is at that point that bacteria, fungi and perhaps other viruses get their way. And you get chronic infection, other viruses emerge, bad bacteria and fungi grow resulting in such things as leaky gut --> Ɛ toxin in circulation, mycoplasma, Cpn infection (which may block receptors and then you get RR), even toenails fungus. This also may result in a further imbalance of gut bacteria, you get into a vicious circle with further weakening immune function etc.

I think the association between EBV infection and CCSVI is relatively straight forward. It is the cartilage (the meningis, tissue of the sinuses) that inflammates first; this also happens for instance in rheuma arthritis. What I found most interesting here is that the internal jugular veins (IJVs) not only relate to an impaired blood flow but that also the Cerebral Spinal Fluid drains in the IJVs. The rest of the brains is just fat, biologically seen, that is poisoned later on by a high concentration of peroxynitrate. You find the mechanism in the above posting on this page.
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Leonard
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Re: A new concept and treatment options for MS

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I was diagnosed with MS in 2004 at the age of 47.
I remember very well that in the years prior to diagnosis, I had a heavy pressure on the sinus, in the back of the throat, painful,
as if I was developing an allergy or hay fever, but I was not allergic and never had hay fever before.
This always occured in the Spring, as I know now when the immune system is low.
MS was diagnosed in the early Summer.

Learning more about the cytomegalovirus http://en.wikipedia.org/wiki/Cytomegalovirus , I now think that the parotid gland was inflammated/infected by the virus. http://en.wikipedia.org/wiki/Salivary_gland
This would explain these painful episodes quite well.
Gradually, the virus must have spread in the brain and inflammated the cartilage/the meningis, and started to affect the endothelium at places where the BBB was broken (CCSVI).
At that time 10 yeas ago there was clearly an RR component i.e. blocking receptors by the virus that the immune system would remove and you get remittance.
Gradually, now over 10 years later, the VZV must have damaged the endothelium and the number of mitochiondria run down, and disability progresses.

Also the occurances earlier in my life are well explained: at 14 years of age, total loss of control of the left hand, lasted for about 10 days, and then resolved completely. At the age of 22, problems with the eyes, I remember particulaly dry eyes,interestingly dry eyes can occur from auto-immune condition http://en.wikipedia.org/wiki/Schirmer's_test . At 29, a limping right leg, lasted again for 10 days or so, with total remittance. At 37, problems with the eyes, was identified as the eye nerves, there must still be a record of this. At 45 numbness on the left hand, a bit on the right hand. But no one suggested MS, MS was completely unknown to me and my family. The virus has been with me for a long time, was surpressed most of the time. But already then at the age of 14 (now 44 years ago) the BBB was breached (CCVSI a birth defect?) and apparently the virus was bounching back and forth between local areas in the brains.

If you explain MS like this, you get a complete, coherent, highly consistent and plausible picture.
For me MS does not have many secrets anymore.
The main thing to do is to get rid of the virus.
Whether to do that by attacking the virus directly or by strengthening the immune system is in my opinion still the big question.
Last edited by Leonard on Mon Sep 08, 2014 12:14 pm, edited 1 time in total.
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Re: A new concept and treatment options for MS

Post by Stillhaha »

Leonard, have you visited http://CPn Help.org/

Idid, shortly after watching this:
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Leonard
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Re: A new concept and treatment options for MS

Post by Leonard »

I reread the book entitled "De CVS-mythe, waarom onze geneeskunde zich geen raad weet met chronische ziekten" (The CFS myth, The Chronic Fatigue Syndrome myth, why our medicine can not cope with chronic diseases) from Dr. Francis Coucke, a free-thinking endocrinologist. Unfortunately, it is in Dutch but I know the author has had many requests for an English copy of the book. So maybe one day there will be an English translation. In any case, the pictures in the book tell a story by themselves.

Overseeing the book, it becomes clear to me that the immune system is getting ever weaker because men is losing its natural habitat (e.g. hygiene on the outside, hardened modern wheat and sterile food on the inside). For the first time in human history, the immune system is no longer trained as it should.

@Stillhaha: thanks for your comment, CPn was on my radar where I think my comment of Wed 3 Sep 12:27am (posting here above) is broadly speaking correct. The case of Cpn is interesting and the bacteria may certainly contribute to the disease (e.g. impact on lining of the veins, blocking receptors). The various stages of the bacteria are intriguing (to all: type www dot CPn Help dot org in your browser without any spaces, I can't get the proper link inserted here either).

Notwithstanding, I think the ground cause for MS is the virus that "occupies" the ever weaker immune system. The results of anti-HIV treatment for MS, some positive stories of patients with valacyclovir, and my own readings for EBV and Herpes simplex demonstrate the link. But there may be some "synergetic" (or may be I should say accumulative) effects of Cpn and the cytomegalovirus/HERV, in the gut. We always think that it is all happening in the brains but that must not necessarily be true. Our biological centre where the main things happen is the gut.

Now the synergetic effects could occur in the gut where a vicious cycle is maintained/strengthened of on the one side virus and Cpn bacteria and on the other side ever weakening immunity. If you tackle the bacteria as was done here , you may break the vicious cycle, strengthen the immune system that then gets control over the virus and thus you see remission as in the case of this women. In this way, you could also explain the case of the Faroe islands.
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Leonard
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Re: A new concept and treatment options for MS

Post by Leonard »

This weblink gives access to various sessions at ACTRIMS/ECTRIMS 2014. I welcome the openness, it shows the tide is changing even in this bastion.
http://www.msboston2014.org/index.php/livestreaming

The presentation on Approaching the cause of multiple sclerosis by Professor David A. Hafler, Yale School of Medicine is interesting. Go to the above website, go to Opening Ceremony Thursday 11 September. The presentation starts after about 40 minutes. I wish to make a few observations on his presentation.

I think CCSVI is a factor. My brother has a mitochondrial energy failure but no MS and has symptoms very similar to mine (incl. gut, compromised immunity, lesions), less energy but better walking, more lesions than me but probably in a different place. I am confident CCSVI is a factor – in fact is the factor - causing the specific inflammation as Dr. Hafler mentions some 5 mins down in his presentation. But there is no mention of CCVSI, as if this would be like "cursing in the church".

There is no mention either of the NO OHNOO hypothesis of Dr. Martin Pall. Still, I think biochemistry is an important component of many immune diseases including MS and mitochondrial energy failure.

He mentions EBV is a central process but then immediately swings over to things like ILx secretion etc. There is no mention of the consequences of a chronic EBV infection, there is no mention of a high load of EBV infected immune complexes and their devastating effect.

He rightly says protecting the gut is critical to MS. He says MS appears to start in the peripheral immune system. We know all this. We also know that the centre of the immune system is the gut. But there is no mention of such things as a possible lack of cortisol on the gut functioning, the role of the endocrine system and of the factor stress caused by induced oxidative stress.

The analysis done is a micro analysis, he gets lost in details, within a narrow scope that neurologists have traditionally claimed as their territory, with underlying thinking that must emanate from the many consults to the long list of companies he mentions in the beginning of his presentation. And although mentioning EBV, peripheral immunity and protecting the gut is hopeful, the wider picture gets lost.

I think we need to detangle MS at a macro-level with fresh eyes, and bring in concepts from other disciplines such as virology, biochemistry, or even endocrinology (e.g. possible role of a lack of cortisol on gut functioning).

In summary: we are ahead. They are learning and become more open. But they are still impeded by old thinking and concepts.
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THIS IS MS

Post by Leonard »

At the age of 22, I was immune compromised (dry eyes, used eye drops in periods for several subsequent years).
I must have had other periods that I was immune compromised (14, 29, 37, 45).
During these periods the virus (Herpes, EBV) could reactivate (I am cytomegalovirus negative).
As such, the virus itself is not programmed to reactivate at specific time intervals but it is the immune system that weakens.

At 45, the immune system weakened again, numbness fingers left hand, a bit on the right hand.
But also something else happened, the parotid gland got infected and inflammated.
And the virus spread in the brain compartment.
The vaccinations (Hepatitis, yellow fever) that I took at in 2000 at the age of 44 (as an immune compromised person) and the massive consumption of fat chocolate (bad diet) were probably not helpful and must have weakened the immune system.
Also the immune system weakened because of age.

At that point, cells in the CNS must have become infected (CCSVI broke the BBB tissue much earlier).
In particular the oligodendrocyte precursor cells (OPCs) were infected.
These oligodendrocytic stem cells and their progenitors are preferred by the virus because they differentiate and help replicate the virus.
At that point, the cells became transgenic for viruses, in particular EBV, VZV and Herpes.
At 47, I had the big flare up with two active lesions, and was diagnosed with RRMS (MS was unknown to me and my family).

The gene transduction occurs during immune deficiency periods (this concerns newly infected cells, does not refer to the 8% transgenic cells from the genome work).
The incorporated viral genes (transgenes) are tolerant to the body or no immune memory against these transgenes has established.
At that point people are still healthy but predisposed to develop MS.

Problems start when they are infected with a microbe that shares epitodes with the transgenes present in the OPCs.
A chronic low-level EBV/VZV/Herpes infection/inflammation will cause such an immunological reaction.
Specific T- and B-cells will pass the CNS and cross-react with the transgenes in the OPCs (my count of EBV/Herpes B-cells is very high).
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.

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 pathogical lesions (sclerotic plaques) typical for MS.

Inflammatory viruses such as VZV will be associated with mild diseases (RR MS) whereas onco viruses such as EBV will be associated with severe diseases as in progressive MS.
Personally I do not exclude the possibility that VZV prepares the path for EBV (microbleedings, angiopathy).

With a special thanks to the eminent immunologist whom I consulted earlier this year; the context is mine, the concept is his.
What is most interesting is that he did his analysis without any knowledge of my situation or the suggested EBV relationship.

The lack of energy in MS and other lesions is a co-morbidity factor caused by the high immune complexes, superoxide, NO, peroxinitrate, poisoning lipids, inhibiting ADP to ATP conversion (Martin Pall).
Hence, the fatigue typical for MS patients may be caused by the same chronic EBV infection but with a completely different underlying mechanism than the plaques in the brains.
Because of high titers, I am eating my muscles and with that also the connection between nerves and muscles; I am sure this is an effect as important as the disconnect in the brains.

In my view, the main components of a therapy are to surpress the virus without reactivating it (e.g. by anti-HIV medication) and to resurrect the immune system (Pender, IgG3).
In the short term, a low-fat diet (Swank, butyrate SCFA to stop EBV replication in the gut) and a 'vegetable' diet (Wahls flavonoids/Campbell fermented foods) will help strengthen the immune system (>90% of the immune system is in the gut).
And NMES to build muscle strength.
I will need to refine the concept on pg 1 accordingly.
Last edited by Leonard on Tue Sep 16, 2014 7:33 am, edited 5 times in total.
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