A new concept and treatment options for MS

If it's on your mind and it has to do with multiple sclerosis in any way, post it here.

Re: A new concept and treatment options for MS

Postby Leonard » Thu Jun 15, 2017 8:10 am

jackblack400 wrote:
How long until we can get access to GNbAC1?

Edit: I've also been thinking about intravenous ATP supplementation. This has been proven to relieve fatigue in cancer patients. If ATP production failure is part of MS why can't that be solved by intravenous ATP supplementation?

Seen this? http://files.shareholder.com/downloads/ ... e_2017.pdf


Jack,

I don't know when GNbAC1 will become available. I picked up the link recently from a Dutch patient forum.

On the ATP supplementation, my physiotherapist suggested exactly the same. Apparently no need for intravenous administration. He used to take it when he was young and as a sportsman ran long distances. I am awaiting further advice.

Thanks for the link to the ATARA presentation. Looks well financed and managed.
Incidently, you see NasoPharyngeal Carcinoma (NPC) and Multiple Sclerosis (MS) mentioned in the same breadth. My grandfarther died from an NPC, I have MS. From my earlier postings, it is clear the two are related and how.
This article is also quite revealing: https://www.ncbi.nlm.nih.gov/books/NBK6235/
quote: EBV is considered a major cause of lymphomas. The putative involvement of the HERV protein in EBV-related growth stimulation of B cells raises the possibility that immunization against the HERV protein, or prevention of its expression via transduction of anti-sense constructs, might inhibit EBV lymphomagenesis. This would be a logical consequence of the results of Sutkowski et al194 There are many reasons to clarify this issue (see below). unquote
Cancer and MS: two sides to the same coin. Interesting, isn't it?

Reg,
Last edited by Leonard on Thu Jun 15, 2017 9:59 am, edited 4 times in total.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Advertisement

Re: A new concept and treatment options for MS

Postby Leonard » Thu Jun 15, 2017 8:14 am

The causes and very mechanisms underlying MS are set out in the Skeleton and synopsis under the links:
general-discussion-f1/topic15188-810.html#p248066
general-discussion-f1/topic15188-795.html#p245692
[and there may be some further useful ideas in here: http://www.mshackathon.nl/wp-content/up ... ressed.pdf ]

The ACTRIMS Feb 2017 Florida Forum covers exactly the same ingredients and would seem to confirm the thinking. See:
https://multiplesclerosisnewstoday.com/ ... o-florida/
The focus ... will be environmental factors, genetics, and epigenetics in MS susceptibility and clinical course. Presenters will disclose recent advances on the relationship between MS susceptibility and diet; the effects of sex chromosomes, hormones, and puberty on the risk of MS and the clinical course of the disease; reveal emerging data on the role of the microbiome in MS development; review controversies regarding the role of viruses in MS; convey state-of-the-art data on genetic and epigenetic factors as risk factors and disease modulators in MS; and other MS-related topics of interest. unquote
or
http://forum2017.actrims.org/forum2017/ ... t-a-glance
http://forum2017.actrims.org/forum2017/ ... -abstracts


The therapeutic options mentioned under the first link above flow directly from a basic understanding of the disease.

The work by GeNeuro and ATARA Bio are commercially driven but would again seem to confirm the above line of thinking. Companies try to find “access points” in the complex cascade, for medication to halt the disease and, to create new shareholder value:
https://www.geneuro.com/data/documents/ ... y-2017.pdf
http://files.shareholder.com/downloads/ ... e_2017.pdf
Or raise profit as here turning one mab into the other: http://www.wheelchairkamikaze.com/2017/ ... l?spref=fb

This is all fine by me, in the end that is how our system works. And for as long as shareholder value is aligned with patient value, there would be no problem. But they are not necessarily. Patients may be better served by the therapeutic options under the first link above, by taking early control of the disease over causal factors (anti-viral, even CCSVI liberation) or by taking control more vigorously and aggressively (chemo/HSCT) rather than control at a later stage by prolongued expensive medication with all its harmful side effects.

I think we have arrived at a point where a major conference should be called. From there, a new dynamic can grow to raise the game. I know it works like that because I have seen it happen several times before (albeit in a completely different area) and was even directly involved in the organization. It could be done again, by academics, policy makers, MS societies. I call on them to get going.
Last edited by Leonard on Mon Nov 27, 2017 12:46 am, edited 23 times in total.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby jackblack400 » Thu Jun 15, 2017 10:40 am

Leonard wrote:
Jack,

I don't know when GNbAC1 will become available. I picked up the link recently from a Dutch patient forum.

On the ATP supplementation, my physiotherapist suggested exactly the same. Apparently no need for intravenous administration. He used to take it when he was young and as a sportsman ran long distances. I am awaiting further advice.



ATP is destroyed in the gut - it is useless taken orally: https://www.ncbi.nlm.nih.gov/pubmed/22510240

This is why it has not gained more prominence as a supplement; people have been taking useless placebo pills. ATP must be supplemented intravenously or intramuscularly. If done so, it may be a game changer.

Thanks for the link to the ATARA presentation. Looks well financed and managed.
Incidently, you see NasoPharyngeal Carcinoma (NPC) and Multiple Sclerosis (MS) mentioned in the same breadth. My grandfarther died from an NPC, I have MS. From my earlier postings, it is clear the two are related and how.
This article is also quite revealing: https://www.ncbi.nlm.nih.gov/books/NBK6235/
quote: EBV is considered a major cause of lymphomas. The putative involvement of the HERV protein in EBV-related growth stimulation of B cells raises the possibility that immunization against the HERV protein, or prevention of its expression via transduction of anti-sense constructs, might inhibit EBV lymphomagenesis. This would be a logical consequence of the results of Sutkowski et al194 There are many reasons to clarify this issue (see below). unquote
Cancer and MS: two sides to the same coin. Interesting, isn't it?

Reg,


EBV has been linked to a whole host of nasties, including, you are right, cancer. But I'm not sure that means we can say MS and cancer are two sides to the same coin. I will read that evolutionary aspects of HERV and disease article, looks very interesting.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2039853/ has a bunch of references to IV ATP supplementation in late stage cancer patients.

https://www.ncbi.nlm.nih.gov/pubmed/10675381 is one:

Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer.

This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC.
jackblack400
Newbie
 
Posts: 7
Joined: Mon Jun 05, 2017 9:28 am

The failure of the system

Postby Leonard » Wed Aug 09, 2017 1:31 am

https://globalfreedommovement.org/the-f ... er-review/

I quote from the Failure of Peer Review:
Most "experts" in medicine are, psychologically speaking, simply engaged in well-paid group thinking and confirmation bias exercises, vigorously affirming and defending their ego's construction of the world ...
Once the public has accepted the scientific establishment's truths, narratives, and designated "experts" then researchers whose research yields results deviating from the accepted norm can be immediately branded as crackpots, lunatics, fringe tools, pseudo-scientists and so on, ... unquote

We must think and should learn to think out of the box, look at other possibilities that leave the traditional medical establishment aside. Because they have constructed a scenario of what might happen (read demyelination and so on...). And the larger the group, the more difficult it is to disconnect oneself from the existing ideas and conclusions. In a sense, it works just like in religions, you automatically assume that all those people around you can not be all wrong.

But they can and they do. All the time.

My vision is here: general-discussion-f1/topic15188-825.html#p248331

MS is not primarily a demyelinating disease, but a failure of mitochondria to produce sufficient ATP for, on the one hand, the ion pump (neuro deficiency) and, on the other hand, the muscles (spasticity). Where at some point the mechanisms become convolved.

The real problem is not MS's etiology and pathogenesis, which are well known. The real problem is the systemic failure of medicine. The challenge is to make a change ...
Last edited by Leonard on Fri Aug 25, 2017 1:01 am, edited 1 time in total.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby frodo » Sun Aug 13, 2017 2:20 pm

Leonard wrote:The causes and very mechanisms underlying MS are set out in the Skeleton and synopsis under the links:

...



Hi Leonard. I have copied your post to the subforum of "etiology and pathology". I think that anyone looking for information about the causes of MS should read it. I hope you don't mind.

I have put it here: ms-etiology-and-pathogenesis-f59/topic29314.html

If you do not like it just tell me and I will remove it.

Thanks for your posts.
User avatar
frodo
Family Elder
 
Posts: 1030
Joined: Wed Dec 02, 2009 4:00 pm

Re: A new concept and treatment options for MS

Postby Leonard » Wed Aug 16, 2017 5:15 am

Hi frodo: you'r welcome to use it as you wish and as you see fit...

@everyone reading here: please spread the message as wide and as far as you possibly can.
Use other fora such as Facebook patient groups to get the message across.
And if you have any contacts there, send it to the press as we will need an actively engaged and critical press to open the discussion.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby Leonard » Thu Oct 05, 2017 3:59 am

As we have seen in the skeleton and the synopsis general-discussion-f1/topic15188-825.html#p248331 , the gut micro biome is a key factor in the etiology of MS. This article in Nature would seem to confirm the thinking and argues that multiple sclerosis patients have a distinct gut microbiota compared to healthy controls:
https://www.nature.com/articles/srep28484
In fact, it is even believed that MS onset could in certain cases be triggered by the micro biome:
https://www.sciencealert.com/multiple-s ... t-microbes

For myself, I was diagnosed with an Inflammatory/Irritatable Bowel Syndrome (IBS) in 2002, followed in 2004 by the MS diagnosis.
But I am not sure whether the micro biome was the issue or perhaps an IgA depletion due to poor working of PPs (EBV B cell related) was lying at the root of my problems.

In any event, Thomas Borody has demonstrated the efficacy for MS of a gut flora transplantation, with PwMS recovering or improving after a gut flora transplantation.

I think that diet alone will not be enough. Some patients who used the Wahls diet to the extreme did not manage to reverse the disease with diet alone. Terry Wahls herself used several cycles of Mitoxantrone prior to her recovery.

This article and other articles suggest that the micro biota regulates T cell functions. While there may be a direct link between the micro biota and the immune system, it cannot be excluded that the reaction is indirect where a healthier micro biota strengthens epigenetic regulation of the cells, reduces cellular expression and by that calms down the immune system.
http://www.pnas.org/content/114/40/10713.full

Whatever is the case, there may be a faster and more effective way than through the microbiome to dampen autoimmunity by interacting directly with T/B cells as with Cladribine. The next posting expands on that idea.
Last edited by Leonard on Mon Oct 16, 2017 1:33 am, edited 3 times in total.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby Leonard » Thu Oct 05, 2017 4:06 am

jackblack400 wrote:Alemtuzumab destroys T cells as well, which is important because B cells aren't the whole story. Ocrelizumab has already been proven to be far inferior to Alemtuzumab and (obviously) HSCT.

Cladribine is like Lemtrada but can cross the blood-brain barrier, it's actually pretty unfortunate that it was pulled from the market for MS. It's something that's going to have to be explored further.

...


Jack, thanks for your postings. Clearly, you are well informed. I am afraid that I did not sufficiently appreciate the comments you made earlier.

As regards your above posting, I would wish to position for a moment Cladribine in between the mabs (e.g. Lemtrada) and HSCT (chemo + stem cell transplantation). Or, in other words, in between on the one hand a light and poorly understood T/B cell depletion regime (mabs don’t enter the CNS so how do they work? ms-etiology-and-pathogenesis-f59/topic29004.html this is why some private neuro clinics administer Rituximab which are rather big particles intrathecal ) and on the other hand a heavy T/B cell depletion regime (HSCT).

Cladribine has recently been approved for highly active RRMS by the EMA
https://www.multivu.com/players/uk/8162 ... ladribine/
http://www.ms-uk.org/european-commissio ... cladribine
https://en.wikipedia.org/wiki/Cladribine
https://www.ncbi.nlm.nih.gov/pubmed/28626781
But besides RRMS, Cladribine is believed to be effective for progressive MS too, and a treatment solution for all.
https://www.ncbi.nlm.nih.gov/pubmed/8643695
http://multiple-sclerosis-research.blog ... o-let.html

The story of Cladribine is fascinating, in more than one respect. Its efficacy for MS was found already back in 1996, but it disappeared from the radar until quite recently.
http://multiple-sclerosis-research.blog ... lls-b.html
Where I don't exclude the possibility that Cladribine for MS is thriving now to give neurologists a 'competitive' alternative for chemo/HSCT which domain is controlled by hematologists.

@ all: I encourage you to read the Barts MS blog under the last link whow….
And to discuss it with your neurologist. That is what I will do.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Neuro degeneration

Postby Leonard » Mon Oct 23, 2017 2:21 am

Just recently, I came across this article on another thread on this forum: Mechanisms of Oxidative Damage in Multiple Sclerosis and Neurodegenerative Diseases
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472775/
[found on general-discussion-f1/topic29496.html#p250120 ]

Now I don’t think the detail is very important but the broad line is all the more important. The thinking fully aligns with the thinking on this thread above.
Interestingly, besides MS, the mechanism of oxidative damage may also underlie many other neurodegenerative diseases such as Alzheimer’s disease.

I think Alzheimer's then works a bit like this:

Specific brain cells don’t trigger internal interferon mechanisms when herpes virinae enter the cell. This deficiency is SNP related; SNPs having a key role in (double stranded) viral DNA detection and anti-viral signalling. The virus can anchor itself in these 'permissible' cells. As there is viral tolerance (you may find ref’s above in this thread), the immune system does not react. People stay healthy but are predisposed.
https://www.researchgate.net/publicatio ... otein_MAVS

In parallel, over time, T/B immune cells get infected with herpes virinae, e.g. T cells with simplex and VZV, B cells by EBV. But even then, people remain healthy but are even more predisposed now.

The problem starts when epigenetic regulation is lost (this is gut microbiome related) and brain cells come to expression. At that point, immune cells find common epitopes causing a cross-reaction. This leads to superoxide (to kill the pathogen), and the initiation of all sort of mechanisms we have seen in the postings above, some of which are also mentioned in the first article.

This causes oxidative stress on the brain cells, mitochondria and then cells die one by one. And one gets holes in the brains and is diagnosed with Alzheimer’s Disease (AD).

Besides neurodegenerative diseases, also other autoimmune diseases like Rheumatoid Arthritis (RA) may find their origin in similar mechanisms:
Oxidative Stress Relevance in the Pathogenesis of the Rheumatoid Arthritis: A Systematic Review
https://www.hindawi.com/journals/bmri/2016/6097417/

Of course, MS is different from AD or RA. A skeleton of MS is given here: general-discussion-f1/topic15188-810.html#p248066
But the fundamentals of all these diseases would seem similar: viral infection, micro-biome dysfunction and cellular expression, (auto)immune reaction, oxidative stress and damage.

A better understanding of disease patterns may also lead us to new therapies for MS and - if the above concept is confirmed - for Alzheimer's and other neurodegenerative and autoimmune diseases. This would include therapies from light (low efficacy) DMTs as interferon and mabs to (high efficacy) more aggressive chemo therapeutic agents (broad T/B cell depletion such as cyclophosphamide and specific B cell depletion such as Cladribine), from microbiota manipulation through diet and probiotics to gut flora transplantation and chemical compounds for more direct control on methylation/epigenetics, from light anti-viral acyclovir based therapies to Highly Active Anti-Retroviral Therapy (HAART) which also seems to work for double stranded herpes.

---

But a total breakthrough requires more than new ideas and concepts, more than lifting old barriers and obstacles.

When building a new model in this area, we can’t just follow a “waterfall” approach. When innovation depends on a series of interdependent innovations – i.e. when innovation is systemic – independent (medical) disciplines will usually not be able to coordinate themselves and to knit those innovations together. In monoliths then like ECTRIMS, innovative ideas will always be squashed, their planning sucks, they keep the sector in a stranglehold. [Post script: to note how far the ECTRIMS/ACTRIMS agenda Oct 2017 Paris is removed from the thinking here. Also to note how the innovative thinking of the ACTRIMS Feb 2017 Florida Forum seems to have entirely evaporated in the Paris meeting]

Scale, integration and new leadership are required to establish and advance new standards.

It is my hope that this thread will provoke new thinking in the sector and stimulate doctors and researchers to enter entirely new pathways.
I am going to draw a line here, it is now for others to pursue.
Last edited by Leonard on Mon Dec 11, 2017 1:51 am, edited 19 times in total.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby vesta » Sun Oct 29, 2017 6:57 am

Greetings:

After noting Professor Dr. George Eberts MS research in 2014, I observed that the birth control pill could be the cause of a statistically significant increase in MS incidence in women over the past 50 plus years. Mike Gaskins calls that idea the « elephant in the room ». (See below).

Birth Control Pills increase the risk of stroke and migraines as well, all vascular issues which point CCSVI as a factor in MS. So how does the vascular factor fit into your bio-chemical narrative ?

http://www.hormonesmatter.com/multiple- ... is-birth...

Author : Mike Gaskins, Jan 9, 2017
Multiple Sclerosis’ Growing Gender Gap

You may wonder how all this talk of T cells and endocrine disruptors translates to actual women. Unfortunately, the results are just as you would suspect. Kaiser Permanente released a study in 2014 disclosing that women who had taken The Pill were 35% more likely to develop Multiple Sclerosis than women who hadn’t. The study also found that women who had used contraceptives but had stopped at least one month before symptoms started were 50 percent more likely to develop MS.
Multiple Sclerosis has always been a discriminatory disease for the reasons outlined by Dr. Rose earlier in this article. However, all indicators point to a dramatic widening of the gender gap since the introduction of birth control pills. According to Gary Cutter PhD., professor of biostatistics at the University of Alabama, in 1940, twice as many women as men had Multiple Sclerosis. By 2000, four out of five MS patients were women. That’s a 50% increase over each decade!
A report published in the Neurology Journal confirmed the increased gender gap as a global trend. After reviewing worldwide epidemiological data, the researchers found that the female-to-male ratio was approximately 1.4 in 1955, and had jumped to 2.3 by the year 2000. Sreeram Ramagopalan, PhD, research fellow at University of Oxford, offered this commentary on the study:
“This intriguing epidemiological phenomenon warrants particular attention because the sex ratio of MS parallels MS incidence, and the increasing frequency of MS among females is a key driver of the increasing prevalence of this devastating disorder worldwide. A change that occurs within a century is too short a time for a genetic cause. This suggests that environmental factor(s) are at work in a sex-specific manner.”
Pardon me for pointing to the elephant in the room, but evidence has already mounted against one particular sex-specific environmental factor that’s been influencing the rise in MS among women over the past 50 years.


Best regards

Vesta
vesta
Family Elder
 
Posts: 555
Joined: Thu Jul 12, 2012 10:10 am
Location: Paris, France

Updated Skeleton MS

Postby Leonard » Sun Jan 07, 2018 3:25 am

Updated Skeleton MS

This recent article from December 2017 fully aligns with and would seem to confirm the thinking on this thread.
https://www.sciencedirect.com/science/a ... 4917300570 on Metabolic defects in multiple sclerosis

As we already saw, (the number of) mitochondria and ATP availability play a key role in the pathogenesis of MS. Mitochondrial energy disturbances aggravated by a higher energy demand because of demyelinated axons cause a neuro deficiency. In the CIS/RR stage, there is an acute mitochondrial failure due to (herpes Zoster - known to be an inflammatory virus) viral activity. Triggered by Mitochondrial AntiViral Signalling (MAVS) proteins, intracellular antiviral interferon and cytokines mechanisms are induced while NF-KB mobilizes specialized T-cells for clean up.
https://www.nature.com/articles/ni.2785
https://www.ncbi.nlm.nih.gov/pubmed/20041442
https://www.researchgate.net/publicatio ... otein_MAVS and refs

Over time, a high oxidative stress develops due to iNOS (re: generally lower blood pressure in MS patients) and EBV B cells (re: generally lower cancer risk in MS patients, EBV which is know to be an onco virus is the major cause for lymphomas in primates). This oxidative stress and high-fat intake (in particular Saturated FA and Trans FA with lipid peroxidation) that inhibits the activity of antioxidant enzymes (e.g. PDI with critical role in neuro degenerative diseases) cause structural damage to the membranes and the endoplasmic reticulum (ER). In turn, with the loss of “healthy intracellular transport pipes”, mitochondria slow down with a lack of ATP as a result causing neuro problems (ion pumps lacks ATP) and neuromuscular problems (low ATP causes soreness and spasticity due to failure to break muscular bonds) and MS progression.
https://www.hindawi.com/journals/mi/2013/137579/
https://www.ncbi.nlm.nih.gov/pubmed/1973220
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472775/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256865/


A new skeleton of MS then looks as follows:

1. in CIS/RR, acute axon energy deficiency (ATP), while extra power needed due to demyelination; in progressive phase: low ATP causes neuro pathway and neuromuscular deficiency incl. soreness and spasticity

2. viral culprit, herpes virinae, hundreds of Millions of years with us, immune system suppresses but never got rid of, herpes even in fish, EBV between 40 and 100 Myears where some pathogenicity is left over, VZV (Zoster)/microbleeds, BBB breach, CCSVI and heavy metal industry, nasopharynx, viral spread/meninges, brain is not immune privileged, viral tolerance

3. autoimmunity, T/B cells get ‘loaded’ with Zoster and EBV respectively, T/B cells and endothelial cells cross react, common epitopes, herpes virinae, viral infection in particular of fast dividing cells, demyelination MBP/OPCs

4. permissible cells got infected, innate immunity and SNPs and MAVS, intracellular interferon and cytokines antiviral mechanisms, MAVS triggers NF-KB, NF-KB controls T cell differentiation and mobilizes specialized T cells, first peak in graph age of onset CIS/RR, SNPs in X-chromosome and gender bias, SNPs in Japanese population

5. around mid age: genome and microbiome co-evolved for 1.5Byears, EBV B cells and Peyer’s Patches, IgA deficiency, leaky gut, IBS, deficient methylation/failure of epigenetic regulation and cellular expression, cross reaction of endothelial cells with B cells, (i)NOS and superoxide EBV B cells, biochemical reaction leads to elevated peroxynitrite, oxidative stress, microglia activation; as the ATP production of mitochondria becomes weaker the inflammatory component that gradually extinguishes over time gets a new chance which explains the second peak in the graph age of onset

6a. biochemistry: neurological trauma and ATP depletion causes stimulation of synaptic neurons, this increases levels of nitric oxide, two distinct positive feedback mechanisms stimulate NDMA receptor activity establishing vicious cycle of oxidative stress, via iNOS to increased NO and peroxynitrite, the longest nerve paths (legs, feet) show most weakness and exhibit earliest and most spasticity, the limps with most neurological trauma shows most progression, vanilloid receptor and temperature effects
6b. elevated peroxynitrite in turn will lower e.g. all reduced folates in the body as a scavenger of peroxynitrite, lowering methylation cycle activity; lowered methylation activity will lead to increased cellular expression, more superoxide from EBV B cells, and more peroxynitrite, further strengthening the vicious cycle [which initially starts and acts at the level of individual cells because NO, superoxide and peroxynitrite have quite limited diffusion distances]

7. lipid peroxidation and cellular metabolic defects, fats (saturated, trans) and inhibition of enzymatic antioxidant activity causes structural changes to Endoplasmic Reticulum, number of mitochondria (note vitamin D relation during growth) is key factor, damage of ER causes ever lower ATP production by mitochondria which results in ion pump failure (neuro deficiency) and spasms (failure to break muscular bonds), air pressure mitochondrial working ATP availability and mobility

8. breaking out of the self-reinforcing vicious cycle of oxidative stress could be done by managing the EBV B cell population by chemo (e.g. cyclophosphamide) with or without HSCT, Cladribine, or mabs, or -ultimately- by hoping that above 60 years of age the B cell population will drop down by itself anyhow, combined with antioxidant treatment (the Pall Protocol http://www.prohealth.com/library/showar ... ibid=17947 ) and low saturated fat diet (as per Roy Swank's protocol https://overcomingms.org/recovery-program/diet/ ). Incidently, Terry Wahls succesfully used the combination of chemo (mitoxantrone in her case) and an anti-oxidant diet to get out of the wheelchair.

The skeleton is up for further discussion. And of course it now needs flesh around the bone. If there are experts or doctors reading here who want to help for instance by drafting a paper along these lines, please send me a PM. Confidentiality guaranteed.
Last edited by Leonard on Mon Mar 26, 2018 2:10 am, edited 12 times in total.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby Leonard » Mon Jan 15, 2018 2:45 am

Hi,

I have amended the previous posting to introduce a self-reinforcing biochemical cycle that ultimately leads to a situation of high oxidative stress (steps 5, 6a, 6b).
To break out of this cycle, therapeutic options could start from both ends: from the side of the endothelial cells or from the side of the T/B cells (step 8 ).

The new skeleton would seem to be a complete and plausible picture of what is MS.
But in the absence of any reaction of substance, I often ask myself questions:
Have I got it all wrong? What am I doing wrong?

Where is this huge medical system? Where are all these stakeholders like MS societies?
And where is politics?

Where should I go and what should I do to get things really resonating?

Thanks for your views,

Regards
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby Leonard » Fri Feb 16, 2018 2:47 am

I think this is the final piece of the puzzle. As a result, it is probably better to reverse step 6a and 6b of the skeleton in the above posting of 7 January and I have done so accordingly.
general-discussion-f1/topic15188-825.html#p251748

If I look at my own experiences as an MS patient, the right leg that was neurologically the weakest ever since the main flare up in 2004 (at age of 47) shows now weakest and thinnest muscles, most spasticity and impairment of mobility. In the beginning, difficulties would only show up after half a mile of running with rapid restoration (ion pump was still replenished with new ATP energy relatively fast) while today problems occur almost instantaneously with little recovery capacity left. Therefore, the neurological trauma left over from the main inflammatory attack in 2004 (and inevitably of some earlier disease activity) had its effects on the further development of the MS disease progression. Why is that?

For the answer we may find important inspiration in the book of Martin Pall entitled “Explaining Unexplained Illnesses”: https://www.amazon.com/Explaining-Unexp ... ed+illness

In particular, the Chapter 2 on Important Components and Their Properties is a must read. The Figure 2.2 on the Neural sensitization cycle explains that the overstimulation of (NDMA) receptors leads to excessive nitric oxide and peroxynitrite production and – as we have seen - as a result ATP (energy) depletion. But the figure also shows another positive feedback loop where nitric oxide acts as a retrograde messenger diffusing to the presynaptic cell stimulating the release of glutamate neurotransmitter, thus leading to increased NDMA receptor stimulation. Hence, a lower energy metabolism (ATP) will result via two distinct mechanisms.

Any time that ATP is depleted (which in my case started very slowly 14 years ago - and probably to a lesser degree even before - by the neurological trauma left over from MS relapses) in cells containing NDMA receptors, these receptors become hypersensitive to stimulation. A mechanism then starts as explained in Pall’s book which makes receptors to be readily stimulated by glutamate thus stimulating the vicious cycle of oxidative stress.

The book refers to evidences that NDMA stimulation causes increase in iNOS activity, NF-KB activity, synthesis of inflammatory cytokines and superoxide levels. In our case, besides the destruction of mitochondrial SOD by peroxynitrite leading to higher levels of superoxide, EBV B cells produce a respiratory burst to generate superoxide. Numerous studies are quoted in the book that provide support for the existence and role in living organisms of many of the important mechanisms proposed to be part the biochemistry cycle and evidences for its plausibility.

Part of the cycle involves vanilloid receptor stimulation leading to increased NDMA stimulation. Interestingly, here may lie a direct explanation for the heat effect that MS patients experience as the vanilloid receptor is known to be stimulated by heat. Thus heat is bad for the MS patient, not only because of direct mobility effects, but also as it would seem to strengthen the nitric oxide production and the vicious cycle mechanism.

Besides the role of the herpes virus and the role of the microbiome on the genome and cellular expression, these new insights could easily mark the end of the beginning of a more holistic understanding of the crucial role of biochemistry in MS and indeed in many other chronic illnesses.

Unfortunately, the new views are so stunning that nobody seems to have the power and or democratic legitimacy needed to take control. While a hundred Billion dollars sector (with pharmaceuticals and academics upfront) has its own inertia, and resists any change. I think here lies the real problem more than the medical complexity and intricacies of MS itself.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

MS unraveled - a metabolic disease of viral origin

Postby Leonard » Fri Mar 16, 2018 1:58 am

MS unraveled - a metabolic disease of viral origin


The disease Multiple Sclerosis (MS) has remained a major unknown for a long time - for too long a time. Ever since the French doctor Charcot diagnosed MS for the first time around 1850, MS is seen as a neurological disease caused by demyelination - say, breaking down the insulation material - around the nerves. For more than a century and a half this hypothesis has been maintained but has never been really understood while the deeper cause of the disease remained unknown.

But recent new insights supported by an abundance of publications in the medical literature change this. MS is no longer that big unknown, is not in its origin a neurological disease, but is a metabolic disease caused by a virus, the herpes virus.

With a better understanding of the etiology of MS and its progressive development, it is now possible to focus very specifically on designing an effective treatment. The biggest problem is therefore no longer the ill-understood or unknown but the weight of the status quo of a sector of more than 100 billion dollars a year that threatens to crush every change.

It is not entirely surprising that it has taken so long. MS is a very complex disease the solution of which brings many new insights together and will ultimately take us much further down the road than the MS disease itself and will usher a paradigm shift in medicine and a new outlook on good human health.


Pathogenic mechanisms in MS

It would take too long to give a detailed medical technical description of MS here. Instead, I want to present a number of cornerstones and how to combine them into a condition for getting MS. Central is - that is the first cornerstone - the herpes virus that has been with us for hundreds of millions of years, it’s even in fish. Our immune system has never been able to get rid of the virus completely, and almost all people have it (causes, for example, cold sores, mononucleosis or Pfeiffer's disease, but also a number of cancers). The virus has merged with us and over time has done very smart things to survive in its host, but also this host (and the cells in that host) has done very smart things to recognize those viruses and destroy them. For example, cells up to the micro-cellular DNA level have certain characteristics in them that enable the cell to recognize foreign viruses such as double stranded herpes and to build up internal defenses, or to mobilize defense from the outside. They are called SNPs for mitochondria anti-viral signaling. The gender bias that we see in autoimmune diseases such as MS originates from SNPs in the X chromosome.

A second cornerstone is the “fusion” of our intestine and the 10 trillion microbiota in that intestine with the cells in our body. This is the result of a co-evolution of 1.5 billion years. The poo in our intestines is not a homogeneous mass but has a large biodiversity with very specific bacteria in certain places in that intestine that are in turn in a certain relationship with the host. And our cells are not those monolithic nicely delineated building blocks as in the construction of a wall, but each of those 60-80 billion cells in our body are fluid biological miracles and the result of more than 1.5 billion years of evolution. Probably they are now more than twice as large as they were 1.5 billion years ago by incorporation of foreign bacteria and viruses. However, the coding capacity - that is the sickening part of it - is mostly suppressed by the evolution. This gives cells a high resistance against new infections. And where that capacity is still present, the intestines play an all-deciding role to "silence" the cells so that pathogenic fragments remain in the cell and remain silent. Given the relationship of the microbiome with SNPs, the intestines further ensure the working of SNPs as mitochondria anti viral messengers.

A third cornerstone that I want to mention is the improved understanding of the biochemistry of the cells. Every biological cell is subject to oxidative stress, say the "rusting" of the cells by oxygen. The cells have anti-oxidant enzymes to prevent this. But in MS, the oxidative stress is so high that cells gradually rust and can not continue to do their normal work. The virus and in particular the defense against the virus by B cells is one of the factors that gives rise to that oxidative stress; another factor is the failure of the nerve cell due to a neurological trauma, for example as a result of an MS flare up. If they no longer do their work properly, the generation of fuel (ATP) in the mitochondria of the cell - the powerhouses of the cell - also stops. And that fuel is a fundamental need without which the ion pump no longer works and we lose the ability to neurologically control our muscles. And the muscle working is also disrupted because there is no more fuel - not only for contraction - but also for the relaxation of the muscle, which manifests itself in increasing spasticity.


MS as a series of interdependent innovations

A combination of these cornerstones makes MS to what it is. In the early phase, 1 of the herpes variants (Zoster, an inflammatory virus) blocks the mitochondria of the nerve cells, so that there arises an immediate shortage of ATP fuel and we see an acute neuro-conduction failure. The immune system reacts, removes the virus and recovery takes place. This is the Relapse Remitting phase. The demyelination that is seen is collateral damage. At a later stage this phenomenon can occur again when the virus gets a new chance because then a number of mitochondria in the cells no longer function properly because the intestine does not keep the cells quiet anymore. This gives a second peak in the graph of the age of onset of MS.

Mitochondria fail successively due to another variant of herpes that slowly increases with age (the Epstein Bar virus or EBV - an onco virus). Our immune system makes B cells in defense against that EBV. That EBV is normally enclosed in the cell (latent there) and there is viral tolerance. But if the cell is no longer silenced by the intestine and is expressed, a cross-reaction takes place between cells in the vein wall and B immune cells. This reaction gives superoxide to kill the pathogen but at the same time also leads to a high oxidative stress due to a biochemical reaction in the veins. The progression in MS is then also triggered by a self-reinforcing feedback mechanism to damaged nerve cells. Together this leads to a progressive disruption of the production of ATP fuel in the cells and the progression of MS.

It is clear that who has more mitochondria in a cell (normally between 1500 and 3000, depending on vitamin D in the cellular growth phase) has a higher resistance to the development of MS, which is exactly what we see. Our modern lifestyle has everything to do with that. There are a number of obvious reasons related to the changing lifestyle why on the one hand our cells and on the other hand our intestinal microbiome are becoming weaker, and - as we actually see – promote a scourge of diseases in our society characterized by autoimmunity.


Can our global medical system merge these innovations?

Deeper insight into the mechanisms that cause MS will turn the medical world upside down and go much further than just MS and - when the mechanisms are understood - eventually lead to a healthier society. But it will be necessary to embrace the new insights all at once and relinquish old dogmas.

In every major system - and that for medicine and healthcare is one - that is not obvious, the system has its own inertia that prevents change. The medical world is also highly fragmented and compartmentalized where it seems that no one has the power and the democratic legitimacy needed to take control.

It is therefore my hope that this article will provide a starting point for change for the benefit of the MS patient, but ultimately for the benefit of all of us and in particular our posterity.


Leonard

is an MS patient who has made this analysis of MS against the background of his own experiences with the help of social forums, the enormous mountain of medical literature on the Internet and some professional advice. Trained as an electrical engineer in the 1970s at Eindhoven University of Technology, he was free to think far beyond the established frameworks. His mind was not set.
Last edited by Leonard on Mon Mar 26, 2018 3:00 am, edited 3 times in total.
User avatar
Leonard
Family Elder
 
Posts: 945
Joined: Fri Dec 18, 2009 4:00 pm
Location: Brussels, Capital of Europe

Re: A new concept and treatment options for MS

Postby David1949 » Sun Mar 18, 2018 2:56 pm

But recent new insights supported by an abundance of publications in the medical literature change this. MS is no longer that big unknown, is not in its origin a neurological disease, but is a metabolic disease caused by a virus, the herpes virus.

Leonard where is the proof of that?

David
David1949
Family Elder
 
Posts: 851
Joined: Mon Aug 23, 2010 3:00 pm

PreviousNext

Return to General Discussion

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users


Contact us | Terms of Service