Anonymoose, why scream NO? Scott, you sound a bit like my neurologist who looked at me as if I would be suicidal. But I am not, I want to live! To the maximum!
I think much of the problems stem from the unknown. Neurologists are no oncologists. They have always dealt with a different type of disease; cancer is deadly, MS is not.
For sure, obscure drivers in the system will not have helped to push forward the use of existing chemo therapy for MS. It was a different disease, in a different field, of a different origin (at least that’s what they thought, we know better now), with different clinicians, and they needed their own set of medication. Specific for MS, just a matter of getting the cash flow going.
And as the world evolved, the spheres hardened.
But as my posting above (on the apparently quite different working mechanisms for the same medication Methotrexate) and as these articles http://www.collective-evolution.com/201 ... -is-false/ and http://www.wheelchairkamikaze.com/2013/ ... e.html?m=1 and http://www.ncbi.nlm.nih.gov/pubmed/25911108 would suggest, there are many things wrong, and there is good reason to doubt many things including on the use or not use of certain medications for MS. This page adds to this picture and makes a link to Rituxan loosing patent protection in 2015 [added 22-6-2015 Or this http://nsnbc.me/2015/06/19/shocking-rep ... -insiders/ ] What a mess...
For MS, for many decades, the right form of control or directorship has been missing. This matter needs governance, with only one objective, that is the patients' interest.
Theoretical Immunology
Re: A new concept and treatment options for MS
Last edited by Leonard on Mon Jun 22, 2015 2:23 am, edited 15 times in total.
Re: A new concept and treatment options for MS
If I ever sound like a neurologist you can shoot me!
Mine stares at me like a possum caught in a torchlight at night.
I only wanted to see what you are currently doing that leads you to consider this path. It might not be the only way.
Regards,
Mine stares at me like a possum caught in a torchlight at night.
I only wanted to see what you are currently doing that leads you to consider this path. It might not be the only way.
Regards,
Re: A new concept and treatment options for MS
Scott, I did not want to be rude. I continue to go back, slowly, steadily. A low fat diet and all the supplementation are just not enough. Also I have no control over the kitchen and lack the discipline to follow a very strict diet. In my stage (late 50's, progressive), I would like to turn to chemo. I have several reports from patients who had Mitoxantrone where the disease kept quiet for quite some time (up to 5 years). I need to get the B cells down and to knock down (herpes) infections, for another 5 years, then the humoral immune system will switch back anyhow. I am an informed patient. I think I have the right to try chemo.
Regards, Leo
Regards, Leo
Last edited by Leonard on Fri May 22, 2015 12:25 am, edited 3 times in total.
Re: A new concept and treatment options for MS
From the other thread on "Possible link between the Hep B vaccine and MS?" http://www.thisisms.com/forum/general-d ... 25792.html
I was vaccinated for Hep B in 1999. In the years 2002-2004, I had a very painful sinus, as if I was developing hay fever, always in Spring.
I was in my mid 40's and never had hay fever before. I think now that the naso pharynx was inflammated and EBV proliferated in the lytic cycle.
In 2003, I had physiotherapy for my neck. I never had physiotherapy before but the neck was awfully painful and stiff.
With hindsight, this was the virus spreading from the naso pharynx through the lymphatic system.
But it did not only go downwards, it went up as well into the cerebral compartment with inflammation of the meninges.
In 2004, I was diagnosed with MS.
The role of the Hep B may be unclear but possibly it weakens the immune system triggering the EBV process in the naso pharynx.
CCSVI is a factor here too because hypoperfusion will weaken the tissue of the pharynx that drains through the IJVs and with that its immune response.
With EBV, EBV infected B-cells and herpes infected cells, the whole cascade of MS starts.
Many good articles can be found on this thread that support the above theory (e.g. search for Frederick Gay).
I offer this theory as an alternative for the Harvard theory and the vaccine-autism theory see http://www.ms-uk.org/vaccinations
I was vaccinated for Hep B in 1999. In the years 2002-2004, I had a very painful sinus, as if I was developing hay fever, always in Spring.
I was in my mid 40's and never had hay fever before. I think now that the naso pharynx was inflammated and EBV proliferated in the lytic cycle.
In 2003, I had physiotherapy for my neck. I never had physiotherapy before but the neck was awfully painful and stiff.
With hindsight, this was the virus spreading from the naso pharynx through the lymphatic system.
But it did not only go downwards, it went up as well into the cerebral compartment with inflammation of the meninges.
In 2004, I was diagnosed with MS.
The role of the Hep B may be unclear but possibly it weakens the immune system triggering the EBV process in the naso pharynx.
CCSVI is a factor here too because hypoperfusion will weaken the tissue of the pharynx that drains through the IJVs and with that its immune response.
With EBV, EBV infected B-cells and herpes infected cells, the whole cascade of MS starts.
Many good articles can be found on this thread that support the above theory (e.g. search for Frederick Gay).
I offer this theory as an alternative for the Harvard theory and the vaccine-autism theory see http://www.ms-uk.org/vaccinations
Last edited by Leonard on Fri May 22, 2015 8:16 am, edited 4 times in total.
-
Anonymoose
- Family Elder
- Posts: 1190
- Joined: Tue Oct 09, 2012 6:33 am
Re: A new concept and treatment options for MS
Leonard,
It's a gut NO...just one of those things you have to listen to for yourself. Your gut might be telling you something different and you should listen to your gut, not mine!
I think if you really feel the methotrexate/rituxan combo is the way to go, you should do it. I'd be extra happy about it if you had a hematologist and infectious disease doctor on board to follow you afterwards and manage any strange events that might come up...like my bizarre labs and really rough 4 months post infusion. Rituxan should be done intrathecally for spms. Have you considered this? There is also talk of lower required dose for efficacy, I think via im injection, that would cut down the expense a lot if you want to also dose outside the cns (the intrathecal does affect systemic levels as well but I decided to double whammy because of my darn gut and frankly I was mad and wanted to beat the ms to a pulp.
).
I'm sure it will take time to even procure the methotrexate/rituxan treatment......
....
......so why don't you (very conservatively) bugger around with some Buhner stuff in the meantime. I'm a week in, just doubled my doses yesterday. I'm herxing a little bit but I think I'm starting to feel my numb hand thing recede at times and all of the weird, usually herx related, leg sensations have gone away. My son gave me a nasty cold so, of course, nothing is as it should be.
You can't just be sitting on your rump letting the disease run free while you try to find someone to provide your dream treatment. Do something else useful in the meantime! You'll just be that much better off when the big plan comes together.
It's a gut NO...just one of those things you have to listen to for yourself. Your gut might be telling you something different and you should listen to your gut, not mine!
I think if you really feel the methotrexate/rituxan combo is the way to go, you should do it. I'd be extra happy about it if you had a hematologist and infectious disease doctor on board to follow you afterwards and manage any strange events that might come up...like my bizarre labs and really rough 4 months post infusion. Rituxan should be done intrathecally for spms. Have you considered this? There is also talk of lower required dose for efficacy, I think via im injection, that would cut down the expense a lot if you want to also dose outside the cns (the intrathecal does affect systemic levels as well but I decided to double whammy because of my darn gut and frankly I was mad and wanted to beat the ms to a pulp.
). I'm sure it will take time to even procure the methotrexate/rituxan treatment......
....
......so why don't you (very conservatively) bugger around with some Buhner stuff in the meantime. I'm a week in, just doubled my doses yesterday. I'm herxing a little bit but I think I'm starting to feel my numb hand thing recede at times and all of the weird, usually herx related, leg sensations have gone away. My son gave me a nasty cold so, of course, nothing is as it should be.
You can't just be sitting on your rump letting the disease run free while you try to find someone to provide your dream treatment. Do something else useful in the meantime! You'll just be that much better off when the big plan comes together.
Re: A new concept and treatment options for MS
Hi Leonard,
I'm basically the same age as you. I was diagnosed 20 years ago. I had my tonsils removed when I was forty, a partial resection of the soft palate as well as a septoplasty. I often wonder if removing all that tissue helped my progression to differ but will never know. The case for EBV wasn't as strong as now and we didn't have work such as Penders to support the argument.
I was extremely well for a very long time after several years of using Valtrex and supplements (even Avonex for a decade) but it didn't stop me having another attack because I didn't pay enough attention to coinfections.
You were able to present a link to some research that showed EBV primes cells to become reactive when another agent is introduced. My own experience is fragments of peptidoglycans (eg from bacterial walls) can trigger an inflammatory response.
I doubt that any of these infections can be totally removed so it becomes an issue of managing the load.
Allergists often refer to "the bucket"- as long as the water in the bucket is below the lip there is no problem. Once the bucket is full, even the small addition to the contents spills over the edge creating a reaction. Make sure your bucket of coinfections is not near the lip.
I have no problem with the objective of your plan but I've lost track of how many times I've said there is no magic bullet and MS is like peeling an onion.
If you're going down this path then I think you need to have a very clear view of what coinfections you may have. Anonymoose is a trail blazer on Rituxumab for MS. It wasn't an easy haul for her.
My approach is different and well documented elsewhere. I am recovering and really all I am dealing with is now comparatively minor. I expect I will fully recover.
Controlling EBV is vital but I slipped on coinfections and paid a price.
Just be very wary of mycoplasmas and gramm negative bacteria.
Regards
I'm basically the same age as you. I was diagnosed 20 years ago. I had my tonsils removed when I was forty, a partial resection of the soft palate as well as a septoplasty. I often wonder if removing all that tissue helped my progression to differ but will never know. The case for EBV wasn't as strong as now and we didn't have work such as Penders to support the argument.
I was extremely well for a very long time after several years of using Valtrex and supplements (even Avonex for a decade) but it didn't stop me having another attack because I didn't pay enough attention to coinfections.
You were able to present a link to some research that showed EBV primes cells to become reactive when another agent is introduced. My own experience is fragments of peptidoglycans (eg from bacterial walls) can trigger an inflammatory response.
I doubt that any of these infections can be totally removed so it becomes an issue of managing the load.
Allergists often refer to "the bucket"- as long as the water in the bucket is below the lip there is no problem. Once the bucket is full, even the small addition to the contents spills over the edge creating a reaction. Make sure your bucket of coinfections is not near the lip.
I have no problem with the objective of your plan but I've lost track of how many times I've said there is no magic bullet and MS is like peeling an onion.
If you're going down this path then I think you need to have a very clear view of what coinfections you may have. Anonymoose is a trail blazer on Rituxumab for MS. It wasn't an easy haul for her.
My approach is different and well documented elsewhere. I am recovering and really all I am dealing with is now comparatively minor. I expect I will fully recover.
Controlling EBV is vital but I slipped on coinfections and paid a price.
Just be very wary of mycoplasmas and gramm negative bacteria.
Regards
Re: A new concept and treatment options for MS
Scott, Anonymoose, thank you for your comments. There is lot of wisdom in your words. Scott, why did you have your tonsils removed and some of the other work done? I am sure there is a relation to MS, see e.g. Frederick Gay. Was it before your diagnosis or after?
Last edited by Leonard on Wed May 27, 2015 12:40 am, edited 1 time in total.
Re: A new concept and treatment options for MS
I start to develop a completely new view on biological life, the evolution of our cells over the last 1 Billion years in a harsh environment, the epi-genetics of our cells and the viral control. I think herpes is an integral part of our evolution path and fully intertwined with cellular immune response and the intracellular accumulation processes leading to increase local release of the anti-inflammatory mediator adenosine. Most probably, we would not have developed as we did without.
http://www.ncbi.nlm.nih.gov/pmc/article ... p00729.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8254024
Like the cellular genome, any virus are subject to epigenetic regulation. But the epigenetic regulation of the virus is weakening due to our profoundly changed living conditions. And we see our immune system, the cells themselves up first, react with inflammation. In the RR phase of MS, the herpes (simplex and Varicella Zoster) virus will block the insulin VDR receptor, the feeding of the mitochondria runs down, the equilibrium of the ion pump can not be maintained, you have a relapse. The immune system removes the infectious agent and there is remittance. In the progressive phase, another phenomenon comes on top. The EBV infected and immortalised B-cells attack the tissue where they find common epitodes, OPCs die, myelin/nerves run down, big oxidative stress, cell machinery runs down, mitochondria fail one by one, the ion pump which needs most energy is the first to fail (nervous path needs more energy than muscular contraction), the nerves run down ...
http://www.ncbi.nlm.nih.gov/pubmed/25473037
You may download the full article if you do a Google search on the full title, and the term ResearchGate and then click on the entry [pdf] Downloaded - ResearchGate
If I copy the full link in here, it does not work so you need to go via the Google search.
I will need to revise the thesis (posting March 26, pg 46) accordingly.
Methotrexate is a potent anti-inflammatory agent. It is promoting the release of the anti-inflammatory mediator adenosine. And probably, there is a whole lot more happening that we not seen or not understood, e.g. with the viral control, how the epi-genetic machinery of the cells improve and will better suppress the virus, how it markedly inhibits leukocyte accumulation in inflammatory pouches, how inflammation will come down...
But the Methotrexate is old from the 1950s and there will be no money in it. So it must have been better for this medical/pharma complex to -consciously or unconsciously- forget about it. But I think its revival is critically needed!
A beautiful expose about how commercial conflicts of interest have led to compromised research and may have been hazardous to our health, you find in Chapter 5 of this book: http://www.amazon.com/University-Inc-Co ... ersity+inc
After you have read this chapter, the world will never be the same.
http://www.ncbi.nlm.nih.gov/pmc/article ... p00729.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8254024
Like the cellular genome, any virus are subject to epigenetic regulation. But the epigenetic regulation of the virus is weakening due to our profoundly changed living conditions. And we see our immune system, the cells themselves up first, react with inflammation. In the RR phase of MS, the herpes (simplex and Varicella Zoster) virus will block the insulin VDR receptor, the feeding of the mitochondria runs down, the equilibrium of the ion pump can not be maintained, you have a relapse. The immune system removes the infectious agent and there is remittance. In the progressive phase, another phenomenon comes on top. The EBV infected and immortalised B-cells attack the tissue where they find common epitodes, OPCs die, myelin/nerves run down, big oxidative stress, cell machinery runs down, mitochondria fail one by one, the ion pump which needs most energy is the first to fail (nervous path needs more energy than muscular contraction), the nerves run down ...
http://www.ncbi.nlm.nih.gov/pubmed/25473037
You may download the full article if you do a Google search on the full title, and the term ResearchGate and then click on the entry [pdf] Downloaded - ResearchGate
If I copy the full link in here, it does not work so you need to go via the Google search.
I will need to revise the thesis (posting March 26, pg 46) accordingly.
Methotrexate is a potent anti-inflammatory agent. It is promoting the release of the anti-inflammatory mediator adenosine. And probably, there is a whole lot more happening that we not seen or not understood, e.g. with the viral control, how the epi-genetic machinery of the cells improve and will better suppress the virus, how it markedly inhibits leukocyte accumulation in inflammatory pouches, how inflammation will come down...
But the Methotrexate is old from the 1950s and there will be no money in it. So it must have been better for this medical/pharma complex to -consciously or unconsciously- forget about it. But I think its revival is critically needed!
A beautiful expose about how commercial conflicts of interest have led to compromised research and may have been hazardous to our health, you find in Chapter 5 of this book: http://www.amazon.com/University-Inc-Co ... ersity+inc
After you have read this chapter, the world will never be the same.
Last edited by Leonard on Thu May 28, 2015 12:15 pm, edited 4 times in total.
Re: A new concept and treatment options for MS
Hi Leonard,
The removal of my tonsillar material is a long story. For a long time, before I was diagnosed, I complained of tiredness, a terrible taste in my mouth and a heavy coating on my tongue. I saw so many people that I lost count and they all said I was tired because I had a stressful job. I knew that wasn't the case. Eventually my sleep was ruined by constantly waking up, gasping for air and every time I opened my mouth to speak I broke into a coughing fit. I kept losing my voice and generally felt terrible. I saw some supposedly clever Ear, Nose and Throat specialists who said I was normal and probably had "some form of asthma". Ultimately I saw a good ENT specialist who said I had laryngitis, pharyngitis, sinusitis and any other "itis" I could think of because my nose was blocked by a deviated septum. He operated to straighten the inside of the nose and said it was like a broken nose. I presume the forceps at birth might have done it as I had no history of breaking it. He hoped that when I started breathing through my nose that the troubles would cease but they did not. Finally he removed my tonsil (which is complex in a forty year old) and said they were like two bags of pus. I wish they had biopsied them but that never happened. I still had engorged material inside my mouth and once the tonsils were removed my uvula (the jiggly bit that hangs down at the back of your mouth) was so big it lay on my tongue and made me gag. To solve that they did a partial resection of the soft palate. That occurred over a two and a half year period and I don't wish those operations on anybody.
My original diagnosis was about six months before the first operation. Maybe it made a difference because so much material was removed in the second and third operations.
The point you make about the anti-inflammatory properties of adonesine is valuable. That's the A in ATP. My use of Q10 and Carnitine is all about recycling ADP to ATP. Adenosine is a purine. The last step in the metabolism of purines is Uric acid. As Uric acid is low in MS then its likely the recycling is faulty. Probably our cells convert 2 ADP into 1 ATP and 1 AMP. The AMP washes out of the cell and the ATP is spent to become ADP and then combines with another ADP to become ATP and AMP again but the purine gets gradually lost to the cell until it is unviable. Uric acid also is a scavenger of peroxynitrite so the cycle worsens over time.
Regards
The removal of my tonsillar material is a long story. For a long time, before I was diagnosed, I complained of tiredness, a terrible taste in my mouth and a heavy coating on my tongue. I saw so many people that I lost count and they all said I was tired because I had a stressful job. I knew that wasn't the case. Eventually my sleep was ruined by constantly waking up, gasping for air and every time I opened my mouth to speak I broke into a coughing fit. I kept losing my voice and generally felt terrible. I saw some supposedly clever Ear, Nose and Throat specialists who said I was normal and probably had "some form of asthma". Ultimately I saw a good ENT specialist who said I had laryngitis, pharyngitis, sinusitis and any other "itis" I could think of because my nose was blocked by a deviated septum. He operated to straighten the inside of the nose and said it was like a broken nose. I presume the forceps at birth might have done it as I had no history of breaking it. He hoped that when I started breathing through my nose that the troubles would cease but they did not. Finally he removed my tonsil (which is complex in a forty year old) and said they were like two bags of pus. I wish they had biopsied them but that never happened. I still had engorged material inside my mouth and once the tonsils were removed my uvula (the jiggly bit that hangs down at the back of your mouth) was so big it lay on my tongue and made me gag. To solve that they did a partial resection of the soft palate. That occurred over a two and a half year period and I don't wish those operations on anybody.
My original diagnosis was about six months before the first operation. Maybe it made a difference because so much material was removed in the second and third operations.
The point you make about the anti-inflammatory properties of adonesine is valuable. That's the A in ATP. My use of Q10 and Carnitine is all about recycling ADP to ATP. Adenosine is a purine. The last step in the metabolism of purines is Uric acid. As Uric acid is low in MS then its likely the recycling is faulty. Probably our cells convert 2 ADP into 1 ATP and 1 AMP. The AMP washes out of the cell and the ATP is spent to become ADP and then combines with another ADP to become ATP and AMP again but the purine gets gradually lost to the cell until it is unviable. Uric acid also is a scavenger of peroxynitrite so the cycle worsens over time.
Regards
Synopsis of MS
Synopsis of MS
1. Immunity
Gut controlled; diet; IFN gamma, IL17, CD4 T cells; cell-mediated immunity; interferon and adenosine; epigenetics and viral control; co-evolved immune system and herpes virus; CCVSI – hypoxia/hypoperfusion; drainage pharynx; immunity compromised; EBV lytic cycle; brain lymphatic system.
2. The viral connection
Double peak in graph age of onset MS; two different mechanisms; inflammatory: VZV angiopathy; microbleedings; receptor blocking; pump /neuro degeneration; RR; arrival CD4+ T lymphocytes; degenerative: EBV takes stage; few inflammations; immune complexes; immortalised B cells; herpes/VZV primed cells triggered by EBV and vice versa; from viral tolerance/predisposition towards disease; common epitopes; subverted immune response by EBV; above 60 decline humoral immunity/B cells
3. Cycle worsens over time
Superoxide; biochemical reaction; peroxynitrite; oxidative stress - oxLDL; the mitochondrial pump; ATP/AMP; energy depletes; adenosine and cellular IFN; lower adenosine and viral control; NO gender bias; ion pump equilibrium; heat effect; VZV/PHN; brain atrophy - cell size- number of active mitochondria; identical twins – vitamin D – number of mitochondria per cell; cell resilience; stressors stimulate iNOS; NF-кB; interlocking cycles; erratic course
4. Therapeutic options
[1. Rituximab to deplete B-cells; Mitotrexate to increase adenosine, boost cell mediated immunity and viral control;
2. detox; antioxidant; neuro muscular electric stimulation to get the virus out of the muscle/nerve cells/PHS; antiviral/Isentress]
Some further detail is given in my thesis in the posting of 26 March on pg 46.
The theory will now need to get flesh around the bone.
Clearly, for me as a semi-literate, that is a challenge.
Professionals like the line of thinking.
But if bits and pieces are wrong, the terminology and the jargon is not theirs, it is not accepted.
Therefore, I hesitate a bit to fill in the detailed text.
Ideally, that would need a professional team.
1. Immunity
Gut controlled; diet; IFN gamma, IL17, CD4 T cells; cell-mediated immunity; interferon and adenosine; epigenetics and viral control; co-evolved immune system and herpes virus; CCVSI – hypoxia/hypoperfusion; drainage pharynx; immunity compromised; EBV lytic cycle; brain lymphatic system.
2. The viral connection
Double peak in graph age of onset MS; two different mechanisms; inflammatory: VZV angiopathy; microbleedings; receptor blocking; pump /neuro degeneration; RR; arrival CD4+ T lymphocytes; degenerative: EBV takes stage; few inflammations; immune complexes; immortalised B cells; herpes/VZV primed cells triggered by EBV and vice versa; from viral tolerance/predisposition towards disease; common epitopes; subverted immune response by EBV; above 60 decline humoral immunity/B cells
3. Cycle worsens over time
Superoxide; biochemical reaction; peroxynitrite; oxidative stress - oxLDL; the mitochondrial pump; ATP/AMP; energy depletes; adenosine and cellular IFN; lower adenosine and viral control; NO gender bias; ion pump equilibrium; heat effect; VZV/PHN; brain atrophy - cell size- number of active mitochondria; identical twins – vitamin D – number of mitochondria per cell; cell resilience; stressors stimulate iNOS; NF-кB; interlocking cycles; erratic course
4. Therapeutic options
[1. Rituximab to deplete B-cells; Mitotrexate to increase adenosine, boost cell mediated immunity and viral control;
2. detox; antioxidant; neuro muscular electric stimulation to get the virus out of the muscle/nerve cells/PHS; antiviral/Isentress]
Some further detail is given in my thesis in the posting of 26 March on pg 46.
The theory will now need to get flesh around the bone.
Clearly, for me as a semi-literate, that is a challenge.
Professionals like the line of thinking.
But if bits and pieces are wrong, the terminology and the jargon is not theirs, it is not accepted.
Therefore, I hesitate a bit to fill in the detailed text.
Ideally, that would need a professional team.
Last edited by Leonard on Sat Jun 20, 2015 1:47 pm, edited 9 times in total.
Re: A new concept and treatment options for MS
Thanks Leonard,
Many years ago, Charcot said that there must be a pathogen to discover. I believe in that, MS perhaps isn't so complicated.
There are new papers about epsilon toxin:
http://www.pubfacts.com/detail/25993478 ... perfringen
Many years ago, Charcot said that there must be a pathogen to discover. I believe in that, MS perhaps isn't so complicated.
There are new papers about epsilon toxin:
http://www.pubfacts.com/detail/25993478 ... perfringen
Re: A new concept and treatment options for MS
Stiti, thanks for your contribution, fascinating stuff...
I am sure there are many things happening in our microcosm that we haven't understood or that we have not even seen. They are of such a complexity with so many factors in the equation and with so many permutations, that it gets almost impossible to get your head around it.
From pg 34 where there was some discussion on the epsilon-toxin, I distill that the toxin leaks from the (bad) gut micro biome into the circulation, and yes it may attach to cells. But what else is there that we haven't seen? Is the virus involved in some way? Is it the combination of transgenic cells and epsilon toxin that puts things in motion? Or is epsilon-toxin to be seen as a phytonutrient that induces anti-oxidants in the body? So many questions, I guess we just don't know...
In my case, I don't have a leaky gut. That can be and was diagnosed affirmatively. I therefore assess the chances that epsilon-toxin leaks into the circulation as quite small. And therefore that my MS is caused by the virus in combination with a number of other factors as in the above Synopsis.
Having said that, if the matter is so complicated, perhaps the approach should be to find out empirically what works. This study from 1995 is interesting and probably did not get the attention it deserves.
http://www.uptodate.com/contents/treatm ... bstract/24
It occurs to me that a thorough risk-benefit analysis of (combined) chemo therapy for MS, as has been called for by some recent papers, has never been done and is urgently needed.
It also occurs to me that the combination of methotrexate and rituximab -a common therapy for rheuma arthritis- has never been tested extensively for MS, at least I can't find it on the Internet. Over the question why not, we can only speculate. But fact of the matter is that a single medication therapy is not good enough. The problem is the virus that you should get under control by boosting the cellular immunity (epigenetics) by methotrexate (and adenosine) and at the same time the B-cells that need to be depleted by rituximab. If you do one and not the other, it works as studies have shown, but just not good enough.
I am sure there are many things happening in our microcosm that we haven't understood or that we have not even seen. They are of such a complexity with so many factors in the equation and with so many permutations, that it gets almost impossible to get your head around it.
From pg 34 where there was some discussion on the epsilon-toxin, I distill that the toxin leaks from the (bad) gut micro biome into the circulation, and yes it may attach to cells. But what else is there that we haven't seen? Is the virus involved in some way? Is it the combination of transgenic cells and epsilon toxin that puts things in motion? Or is epsilon-toxin to be seen as a phytonutrient that induces anti-oxidants in the body? So many questions, I guess we just don't know...
In my case, I don't have a leaky gut. That can be and was diagnosed affirmatively. I therefore assess the chances that epsilon-toxin leaks into the circulation as quite small. And therefore that my MS is caused by the virus in combination with a number of other factors as in the above Synopsis.
Having said that, if the matter is so complicated, perhaps the approach should be to find out empirically what works. This study from 1995 is interesting and probably did not get the attention it deserves.
http://www.uptodate.com/contents/treatm ... bstract/24
It occurs to me that a thorough risk-benefit analysis of (combined) chemo therapy for MS, as has been called for by some recent papers, has never been done and is urgently needed.
It also occurs to me that the combination of methotrexate and rituximab -a common therapy for rheuma arthritis- has never been tested extensively for MS, at least I can't find it on the Internet. Over the question why not, we can only speculate. But fact of the matter is that a single medication therapy is not good enough. The problem is the virus that you should get under control by boosting the cellular immunity (epigenetics) by methotrexate (and adenosine) and at the same time the B-cells that need to be depleted by rituximab. If you do one and not the other, it works as studies have shown, but just not good enough.
Re: A new concept and treatment options for MS
Hi Leonard,
I suppose that talking about MS etiology is like talking about lottery winning numbers before they are published...
Anyway more news about epsilon toxin published on 16th june:
http://mbio.asm.org/content/6/3/e02513-14
I suppose that talking about MS etiology is like talking about lottery winning numbers before they are published...
Anyway more news about epsilon toxin published on 16th june:
http://mbio.asm.org/content/6/3/e02513-14
Re: A new concept and treatment options for MS
Stiti,
Gut commensal microorganisms affect immunological reactions. In the years prior to being diagnosed with MS, I eat loads of chocolates and fat chocolate ice creams, every day again. I guess to boost the metabolism. A very unhealthy diet. Remarkably, I know others with MS in senior positions who did exactly the same thing.
My gut was bad at that time, already for some years, and by the very unhealthy diet probably got even worse. I guess it may have been leaky at the time.
I did not relate the things at the time. Only many years later, after being diagnosed with MS, when I followed a low saturated fat (Swank) diet for half a year or so, the gut stabilized – completely unexpected. And it was even later that I started to realize the influence of a healthy gut on immunity.
When a representative model of the human gut eco-system was established in mice, switching from low-fat, plant polysaccharide-rich diet to a high fat, high sugar “Western” diet shifted the structure of the microbiota of these “humanized” mice in a single day and changed the metabolic pathways in the micro biome and its gene expression.
http://stm.sciencemag.org/content/1/6/6ra14
Germ free mice induced for EAE produced lower levels of proinflammatory cytokines IFN-gamma and IL17 in both the intestine and the spinal cord and displayed reciprocal increase of CD4 T cells.
http://www.pnas.org/content/108/Supplem ... nsion.html
Some microbe families from the gut microbiota however promote the inflammatory cascade in the CNS. The strongest here being the unculturable Clostridium family of which the Segmented Filamentous Bacteria is the most active. See e.g. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses
http://www.ncbi.nlm.nih.gov/pubmed/19833089
This observation matches well with the recent article on epsilon toxin: Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination
http://mbio.asm.org/content/6/3/e02513-14
It has been suggested for decades that micro organisms contribute to the pathogenesis of MS. See e.g. the article by Frederick Gay Bacterial toxins and Multiple Sclerosis. The article from 2007 already noted "Data is reviewed which shows that the CSF and extra-cellular fluid circulation is bi-directionally linked to the lymphatic drainage channels of the nasopharyngeal mucosa. While this provides a facility by which the CNS may mount immunological responses to antigenic challenges from within, it is also a route by which products of nasopharyngeal infection may drain into the CNS and be processed by the immune cells of the meninges and Virchow-Robin perivascular spaces.”
http://www.unboundmedicine.com/medline/ ... _Sclerosis_
I wonder whether the above article from F. Gay comes close to other thread on this forum on CNS lymph vessels found. Brain is not immune-privileged, see e.g.
http://www.thisisms.com/forum/general-d ... 26449.html
From F. Gay we have also seen this article, and connected it to EBV proliferation from the pharyngeal cells.
http://www.msard-journal.com/article/S2 ... 9/abstract
This article is possibly also of interest because it shows what toxins can do: Systemic administration of Pertussis toxin (PTX) abrogates T cell tolerance .. and causes experimental autoimmune encephalomyelitis (EAE).
http://www.ncbi.nlm.nih.gov/pubmed/20398738
This brings us in the domain of cellular biology. Pertussis toxin and adenylate cyclase toxin are two important virulence factors of Bordetella pertussis, the bacterial cause of the respiratory disease pertussis or whooping cough. In addition to studies on the structure, function and role in pathogenesis of these two toxins, they are both used as cell biology tools for a variety of applications owing to their ability to enter mammalian cells, perform enzymatic activities and modify cell signaling events.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851156/
It seems that many things come together here in the big melting pot. The central role of the gut in immunity, the direct link between the brain and the immune system and the lymphatic drainage of the brain, the role of the pharynx, the co-evolution of the herpes virus and cellular immunity, toxic bacterial cell molecules and transportable proteins triggering intra-cellular events, the role of oxidative stress and cellular antioxidant mechanisms, there is an array of health issues that must be reconsidered. All will have their role to play in unravelling MS.
There are many things to think about.
Gut commensal microorganisms affect immunological reactions. In the years prior to being diagnosed with MS, I eat loads of chocolates and fat chocolate ice creams, every day again. I guess to boost the metabolism. A very unhealthy diet. Remarkably, I know others with MS in senior positions who did exactly the same thing.
My gut was bad at that time, already for some years, and by the very unhealthy diet probably got even worse. I guess it may have been leaky at the time.
I did not relate the things at the time. Only many years later, after being diagnosed with MS, when I followed a low saturated fat (Swank) diet for half a year or so, the gut stabilized – completely unexpected. And it was even later that I started to realize the influence of a healthy gut on immunity.
When a representative model of the human gut eco-system was established in mice, switching from low-fat, plant polysaccharide-rich diet to a high fat, high sugar “Western” diet shifted the structure of the microbiota of these “humanized” mice in a single day and changed the metabolic pathways in the micro biome and its gene expression.
http://stm.sciencemag.org/content/1/6/6ra14
Germ free mice induced for EAE produced lower levels of proinflammatory cytokines IFN-gamma and IL17 in both the intestine and the spinal cord and displayed reciprocal increase of CD4 T cells.
http://www.pnas.org/content/108/Supplem ... nsion.html
Some microbe families from the gut microbiota however promote the inflammatory cascade in the CNS. The strongest here being the unculturable Clostridium family of which the Segmented Filamentous Bacteria is the most active. See e.g. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses
http://www.ncbi.nlm.nih.gov/pubmed/19833089
This observation matches well with the recent article on epsilon toxin: Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination
http://mbio.asm.org/content/6/3/e02513-14
It has been suggested for decades that micro organisms contribute to the pathogenesis of MS. See e.g. the article by Frederick Gay Bacterial toxins and Multiple Sclerosis. The article from 2007 already noted "Data is reviewed which shows that the CSF and extra-cellular fluid circulation is bi-directionally linked to the lymphatic drainage channels of the nasopharyngeal mucosa. While this provides a facility by which the CNS may mount immunological responses to antigenic challenges from within, it is also a route by which products of nasopharyngeal infection may drain into the CNS and be processed by the immune cells of the meninges and Virchow-Robin perivascular spaces.”
http://www.unboundmedicine.com/medline/ ... _Sclerosis_
I wonder whether the above article from F. Gay comes close to other thread on this forum on CNS lymph vessels found. Brain is not immune-privileged, see e.g.
http://www.thisisms.com/forum/general-d ... 26449.html
From F. Gay we have also seen this article, and connected it to EBV proliferation from the pharyngeal cells.
http://www.msard-journal.com/article/S2 ... 9/abstract
This article is possibly also of interest because it shows what toxins can do: Systemic administration of Pertussis toxin (PTX) abrogates T cell tolerance .. and causes experimental autoimmune encephalomyelitis (EAE).
http://www.ncbi.nlm.nih.gov/pubmed/20398738
This brings us in the domain of cellular biology. Pertussis toxin and adenylate cyclase toxin are two important virulence factors of Bordetella pertussis, the bacterial cause of the respiratory disease pertussis or whooping cough. In addition to studies on the structure, function and role in pathogenesis of these two toxins, they are both used as cell biology tools for a variety of applications owing to their ability to enter mammalian cells, perform enzymatic activities and modify cell signaling events.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851156/
It seems that many things come together here in the big melting pot. The central role of the gut in immunity, the direct link between the brain and the immune system and the lymphatic drainage of the brain, the role of the pharynx, the co-evolution of the herpes virus and cellular immunity, toxic bacterial cell molecules and transportable proteins triggering intra-cellular events, the role of oxidative stress and cellular antioxidant mechanisms, there is an array of health issues that must be reconsidered. All will have their role to play in unravelling MS.
There are many things to think about.
Last edited by Leonard on Tue Jun 23, 2015 6:32 am, edited 3 times in total.
Epsilon toxin specifically targets myelin forming cells
The article suggests epsilon toxin specifically targets the myelin-forming cells, a selectivity for oligodendrocytes, where apparently other cells in the CNS are unaffected. http://mbio.asm.org/content/6/3/e02513-14
I am not sure whether this is a coincidence but the herpes/EBV virus also prefers the OPCs, the precursor cells of of the oligodendrocytes. I was told the virus prefers these cells, just like the cells in the bone marrow, because it helps them to proliferate as each time the cell divides, the virus duplicates as well.
Could there be a connection? That is to say, could it be that epsilon toxin, but perhaps other bacterial cell molecules and transportable proteins as well e.g. from the naso pharynx and/or from the gut, trigger transgene / herpes EBV primed cells to activate intra-cellular events leading to the release of pro-inflammatory lipid mediators, enzymatic activities and modified cell signaling events? And -eventually- a loss of epi-genetic control of the virus and cell death? In other words, is it 'synergetic effects' of virus and bacterial toxins working together that Buhner talks about in his book Healing Lyme disease coinfections that misguide or reduce the effectiveness of the immune system? E.g. through sharing segments of DNA?
Already early in my early 20's, the plantar reflex of my feet showed the positive Babinski sign. https://en.wikipedia.org/wiki/Plantar_reflex And during that same examination, the doctor noted a difference between my right and my left leg. The muscles in the left leg where better developed. I remember, the doctor found it very weird, he had never seen this before. Was there already neurological damage at that time?
I was diagnosed at 47. In a few months time, I will be 59, still walking, but the right leg is clearly worse than the left.
Now clearly, I can not recall any problems with my gut in my 20's or 30's. These problems only started when I had passed 40. So were the early problems caused by naso pharynx infections, noting that CCSVI/the bad drainage must have been there already and was most likely a birth defect -at least half of it, that is the sharp truncation in the right IJV, the left IJV showed obstruction/narrowing behind the ear which may have been viral consequence that arose later on? Not impossible at all..
I am not sure whether this is a coincidence but the herpes/EBV virus also prefers the OPCs, the precursor cells of of the oligodendrocytes. I was told the virus prefers these cells, just like the cells in the bone marrow, because it helps them to proliferate as each time the cell divides, the virus duplicates as well.
Could there be a connection? That is to say, could it be that epsilon toxin, but perhaps other bacterial cell molecules and transportable proteins as well e.g. from the naso pharynx and/or from the gut, trigger transgene / herpes EBV primed cells to activate intra-cellular events leading to the release of pro-inflammatory lipid mediators, enzymatic activities and modified cell signaling events? And -eventually- a loss of epi-genetic control of the virus and cell death? In other words, is it 'synergetic effects' of virus and bacterial toxins working together that Buhner talks about in his book Healing Lyme disease coinfections that misguide or reduce the effectiveness of the immune system? E.g. through sharing segments of DNA?
Already early in my early 20's, the plantar reflex of my feet showed the positive Babinski sign. https://en.wikipedia.org/wiki/Plantar_reflex And during that same examination, the doctor noted a difference between my right and my left leg. The muscles in the left leg where better developed. I remember, the doctor found it very weird, he had never seen this before. Was there already neurological damage at that time?
I was diagnosed at 47. In a few months time, I will be 59, still walking, but the right leg is clearly worse than the left.
Now clearly, I can not recall any problems with my gut in my 20's or 30's. These problems only started when I had passed 40. So were the early problems caused by naso pharynx infections, noting that CCSVI/the bad drainage must have been there already and was most likely a birth defect -at least half of it, that is the sharp truncation in the right IJV, the left IJV showed obstruction/narrowing behind the ear which may have been viral consequence that arose later on? Not impossible at all..
Last edited by Leonard on Tue Jun 23, 2015 6:28 am, edited 3 times in total.