Hi Leo,
The more I look at it the more it looks to me that ATP is not just about energy, it's the key to the body's ability to self regulate. When it depletes or when it is released from the cell inappropriately things go wrong with us that other people seem to manage successfully. The gradual accumulation of radical damage catches up with them but we get hit with extreme effects. Boosting ATP formation and function will be the only goal when everything is distilled to a single objective. Sinatras book is the hardest thing I've read but it's also the best. He has jammed it with detail but unfortunately skims over a couple things and spends too much time on anecdotal evidence. He is talking to cardiologists so he presentation is justifiable. I could see a read through to MS all through it but it's not his area. If you can have a read I think you'll find it useful.
Regards
Theoretical Immunology
Re: THE PROTOCOL
Thank you PN for this hybrid regimen, very useful. How are you doing? Have you stabilised or have you been able to stop progression?PointsNorth wrote:Thanks Leo - a nice (much needed) summary of the Whals Regimen. I am on a hybrid regimen involving:Leonard wrote:I think a therapy for MS should look a bit like this (not necessarily in the order of importance, e.g. Terry Wahls recovered by steps 5 and 6 only):
5. Capture free radicals (vit B and D, CoQ10, MitoQ, more vegetables/antioxidants/flavonoids)
see e.g. pg 14 - 17 of: http://www.ms-uk.org/files/npwm_2009_0053.pdf
6. Stimulate muscle strength (exercise, NMES)
see e.g. pg 14 - 17 of: http://www.ms-uk.org/files/npwm_2009_0053.pdf
And add to that a good dose of hope.
High Dose vit D 60Kiu day
Magnesium w. B6
CoQ10 300mg
Some Zinc & Omega3
Transdermal B12 (thinking that formulation with MultiBs could be best)
Extra B2
Soon to add Lecithan
Last edited by Leonard on Tue Dec 02, 2014 4:06 am, edited 2 times in total.
Re: A new concept and treatment options for MS
Thank you Scott for this reference, I will get the book. Judging from its table of contents that you can see on Amazon, it looks fascinating. I am sure you are right that the ATP is about much more than just energy. Where indeed such things as ribose, carnitine, and CoQ10 have a profound effect on the whole metabolism. I was recently pointed to the possible benefits of Erythropoietin (EPO) http://en.wikipedia.org/wiki/Erythropoietin for MS patients, which seems to fall into that same category.Scott1 wrote:Hi Leo,
The more I look at it the more it looks to me that ATP is not just about energy, it's the key to the body's ability to self regulate. When it depletes or when it is released from the cell inappropriately things go wrong with us that other people seem to manage successfully. The gradual accumulation of radical damage catches up with them but we get hit with extreme effects. Boosting ATP formation and function will be the only goal when everything is distilled to a single objective. Sinatras book is the hardest thing I've read but it's also the best. He has jammed it with detail but unfortunately skims over a couple things and spends too much time on anecdotal evidence. He is talking to cardiologists so he presentation is justifiable. I could see a read through to MS all through it but it's not his area. If you can have a read I think you'll find it useful.
Regards
Re: A new concept and treatment options for MS
Actually, it's funny, the Sinatra book talks about a 'cardiac virus' damaging heart tissue that has poor conditions/blood flow - I guess it is meant in a metaphorical sense - but it might well turn out that it is literally a virus, the VZV that gets is chance, just as in MS in areas in the brains with poor conditions/blood flow... wow
Last edited by Leonard on Wed Dec 03, 2014 12:22 am, edited 1 time in total.
Re: A new concept and treatment options for MS
Further to the previous posting on the key role of the cellular machinery and heat sensitivity, I think that the whole-brain atrophy observed in MS patients is also caused by the failing cellular machinery.
As gates are jammed and cellular respiration is impaired, mitochondria will fail one by one (out of the 1500 - 3000 per cell).
As we go along, cells will shrink in size, and the brain will shrink as a whole.
Atrophy of any tissue means a decrement in the size of the cell http://en.wikipedia.org/wiki/Cerebral_atrophy
see also http://www.thisisms.com/forum/general-d ... 25637.html
On the basis of our learnings, I have prepared the following manuscript that I am now trying to get published.
As the thinking breaks with everything that we have seen, getting the manuscript accepted for publication is not so easy.
Therefore, I put it here (in the following posting) as a pre-publication.
As gates are jammed and cellular respiration is impaired, mitochondria will fail one by one (out of the 1500 - 3000 per cell).
As we go along, cells will shrink in size, and the brain will shrink as a whole.
Atrophy of any tissue means a decrement in the size of the cell http://en.wikipedia.org/wiki/Cerebral_atrophy
see also http://www.thisisms.com/forum/general-d ... 25637.html
On the basis of our learnings, I have prepared the following manuscript that I am now trying to get published.
As the thinking breaks with everything that we have seen, getting the manuscript accepted for publication is not so easy.
Therefore, I put it here (in the following posting) as a pre-publication.
Last edited by Leonard on Wed Dec 03, 2014 12:18 am, edited 1 time in total.
Towards a revolution in healthcare
The debate on autoimmunity at a crossroads - on choices for real change
I am an MS patient who was trained in a technical discipline. But when I was diagnosed with MS in 2004, I became extremely motivated to unravel the disease that increasingly ruled my life and started to learn more about the disease. In the meanwhile, with my own experiences as an MS patient in mind and with the help of the vast amount of medical literature available on the Internet, some professional advice and the social and patient fora, I have become a semi-literate. The journey has led me to a new understanding of the disease that is presented here. You find more background and literally hundreds of references in the medical literature on this thread.
Paradigm changes often come unexpected and from the outside, and are motivated either by young people who are new to the field or by people who look with fresh eyes at the problem. This has definitely helped me because I did not have to unlearn, my mind was not set by old dogmatic believes that every medical student has to learn if he wants to pass his exams, and I could see new connections and concepts that others perhaps could not see, believe, accept or propose.
A critical need to open the mind set
Autoimmune diseases like Crohn’s Disease and Multiple Sclerosis (MS), in which the immune system attacks its own body rather than predatory invaders, affect 5-20% of the global community. The current scourge of immune diseases points to a growing problem of an overall weakening society. [more on scope of problem, statistics, hits ever younger people] If the trend is not changed, consequences for the general health of our population and that of future generations may be far reaching.
We must spot current trends in societal health, take these trends extremely serious and investigate what is driving them as a matter of urgency. To this end, we should question the status-quo on autoimmunity.
However, as the weight of the status-quo is so immense, every change proposal is at risk to collapse under that weight. Significant systemic problems are pervasive and hamper a course towards investigating or even considering alternative views. The risk is a stagnation while the debate does not get a fair chance and may be dead even before it has started.
In order to find a way out of the impasse, it will be critically necessary that the matter is approached with an open mind, and that alternative views on autoimmunity are explored and new connections investigated with urgency and with force.
The viral connection
The current scourge of immune disease is explained by an immune system that gets ever weaker. There is a multitude of underlying factors: an unhealthy diet, poor quality food (e.g. engrainisation, ‘hardened’ wheat, soil depletion, a lack of flavonoids which generate antioxidants, hydroponic plant growth), a lack of immune system training (e.g. extreme hygiene and indoor/office life, we forgot about fasting which is deep in the Old testament, people who work outdoors are generally much healthier), and stress in a very broad sense. The immune system also weakens with age.
When the immune system weakens, the herpes virus emerges can surface [herpes is a family of viruses]. Most of the human population have it and it has been with us for millions of years, even when we were still apes hanging in the trees of Africa. But all the time it was kept in control by a good functioning immune system. However, the last 50 years, something new is happening that has not been seen before in the history of mankind. Our living conditions have changed so profoundly that the immune system does not keep the virus in check anymore.
The viral tolerance theory - autoimmunity explained
During periods that people are immune compromised (can be the fetal period, the period of the newborn and immune deficient periods), the virus can incorporate some of its genes in the DNA of permissible cells. As such, the virus itself is not programmed to reactivate at specific time intervals but it is the immune system that weakens.
The gene transduction occurs during immune deficiency periods. The incorporated viral genes (transgenes) are tolerant to the body or no immune memory against these transgenes has established.
In MS, in particular the oligodendrocyte precursor cells (OPCs) will be infected. These oligodendrocytic stem cells and their progenitors are preferred by the virus because they differentiate and help replicate the virus. Also for that reason the bone marrow will be infected. Chronic cerebro spinal vascular insufficiency (CCSVI or narrowed internal jugular veins) is a factor – most probably a birth defect - that broke the BBB tissue in an earlier phase. [in rheuma arthritis it is the cartilage of the joints, in MS infection of the cartilage of the sinuses is an issue that helps spreading the virus, for Crohn’s disease permissible cells are in the intestine]
People with transgenes in their body are healthy but predisposed to develop a disease. Predisposed people become diseased when they are infected with a microbe that shares epitodes with the transgenes present in the transgenic cells and will cause an immunological reaction. A chronic low-level EBV infection is suspect in MS but also a Hepatitis vaccinations has been suggested as a trigger. Crohn's disease is associated with measles.
In MS, specific T- and B-cells will pass the CNS and cross-react with the transgenes in the OPCs. Due to this cross-reaction, many OPCs will die which leads to a diminishing number of OPCs, of dendrocytes and a reduced myelination of neurons. EBV resides in the B cell and immortalizes it. So in reaction, the immune system produces more and more. [The count of EBV/Herpes immune cells in my circulation is very high, about 20 x max.]
During this cross-reaction, many mediators will be released by the infiltrating T-cells. This will increase angiogenesis and cause hyperproliferation of surrounding tissue cells in the CNS which in turn causes the pathological lesions (sclerotic plaques) typical for MS.
The symptoms of MS will be mild in relapse-remitting MS but severe in progressive MS depending on the kind of virus that has incorporated part of its genome in the oligodendrocytic stem cells. Inflammatory viruses such as VZV will be associated with mild diseases whereas onco viruses such as EBV will be associated with progressive MS. [I do not exclude the possibility that the VZV mechanism (microbleedings, angiopathy, acute inflammation by blocking of receptors) is followed later on by the EBV mechanism (immortalized B-cells, autoimmunity of transgenic cells) where precisely the kick-in of this latter mechanism explains the second peak in the graph of age of onset of MS. ]
The biochemical reaction hypothesis – the fatigue and brain atrophy explained
Besides the immune reaction against the OPCs, the high load of immune complexes has a second important effect. This is all about fatigue, deterioration of the cell machinery and cellular respiration, disabling glycaldehyde-3 phosphate, the peroxydisation of lipids and other disturbances crucial to the progression of MS but not necessarily major demyelination.
The immune cells have substantial super-oxygen generating capability. The superoxide reacts with the nitric oxide and forms peroxynitrate. The peroxynitrite is by far the worst free radical which causes huge oxidative stress, immune response, jams the gates/mitochondria of the cells, causes effects on the mitochondrial electron transport chain, electron pump inactivation, inhibits ADP to ATP conversion and depletes energy in the form of ATP. And it poisons fat tissue and causes lesions where the brains, biologically seen, are just a lump of fat. I think it also causes what is called herpetic neuralgia where fibromyalgia is not far away.
The lack of energy in MS and other lesions is thus a co-morbidity factor caused by the VZV angiopathy in combination with the EBV high immune complexes. As the number of active gates goes down, we see an increasingly big temperature effect in patients with MS and a loss of muscle strength and sensitivity in the periphery which is an effect possibly as important as the disconnect in the brains. And as cells shrink in size because gates/mitochondria fail, it causes whole brain atrophy. Hence, the typical fatigue, weakening of muscles and whole-brain atrophy observed in MS patients is partly caused by the chronic VZV/EBV infection but with a completely different underlying mechanism than the demyelinating plaques in the brains.
[an extensive analysis of my blood revealed that there are only a few parameters out of their normal margin: that is the high concentration of herpes/EBV immune complexes and high titers of muscles, hence I am eating my own muscles and with that also the connection between nerves and muscles]
In parallel to the MS plaques and immune cell activation in the brain, the NF-KB is triggered by the biochemical cycle mechanism, causing elevated cytokines that contribute to raising the inflammation and Th activity. Where, at some point, mechanisms become all convolved.
A general dysregulation of the metabolism – interlocking vicious cycles
The virus is causal and leads to a general dysregulation of the metabolism.
The problem of disease progression can not be solved by metabolic factors. For sure, hormones are an influence. Hormonal deficiencies often relate to symptoms belonging to lupus, CFS or fibromyalgia or other auto immune diseases. [In my case some hormones were on the low end including cortisol and – as a derived product - testosterone]
At some point in the autoimmune disease process, the HPA axis will be affected causing hormonal deficiencies starting with cortisol. This will have its effects on the gut and further weaken the immune system, thus causing a vicious cycle. [to note: gut problems often precede an MS diagnosis; 90% of the immune system resides in the gut; the role of bacteria in the gut which may help solve autoimmune diseases such as e.g. diabetes T2, the central role of the gastro intestinal tract for good immunity]
While hormones are an influence, administration with hormones (e.g. cortical and DHEA) won’t be convincing. Without tackling the virus and the viral infection, the problem will persist.
This is also true for infection by bacteria and fungi including Borrelia and Cpn, toxoplasmose and such things as toe nail fungus which get their chance when the immune system is fighting the virus [IgG3 depletion]. The infection will aggravate the situation and challenge the immune system further. It is important to get rid of all bacterial infections but fighting the infections alone won’t be enough.
Besides the endocrinological disorders and infectious diseases, there is yet another loop, from the psychological to the physiological. (Short term) stressors that initiate cases of multisystem illnesses act by stimulating nitric oxide synthase (NOS) activity and consequently produce increased levels of nitric oxide and its oxidant product peroxynitrite. Initiation is converted into a chronic illness and a lowered energy metabolism through the activation of vicious cycle mechanisms through which chronic elevation of nitric oxide and peroxynitrite is produced and maintained. All three nitric oxide synthases have been shown to be involved (eNOS, nNOS and iNOS).
The NF-KB is triggered by the biochemical cycle mechanism. The increased NF-KB activity will lead to increased iNOS activity by stimulating through the inflammatory cytokines IL's, TFN and IFN the activity of the iNOS gene itself.
There is a combination of stability and instability, positive and negative feed back loops, leading to what is essentially inflammatory biochemistry. [vicious cycle is the NO/OHNOO hypothesis – Martin Pall]
MS is therefore a subtle multi factorial disease where a number mechanisms and vicious loops are convolved. This explains the erratic course of the disease, and the large variety of symptoms and disease progression seen in MS patients.
Towards to a new paradigm for autoimmune diseases
In our current system for medicare, we see a very large number of overlapping autoimmune diseases with different names. Every expression of a neurological set of symptoms got its own name, based on several types of observations. And we see various signs and symptoms that are overlapping e.g.: slowly progressive symmetric distal sensor motor neuropathy, muscle loss, difficult urine retention, pain worse at night, gender bias, fatigue, distorted Ca levels and inactivated pump mechanisms.
But in fact, a bigger common scheme is underlying. A scheme that encompasses the wide variety of observations, their patterns of case initiation, their chronic nature and many of their shared and unique symptoms and signs of the chronic phase of the disease. A scheme that explains many unexplained observations and the multiple similarities of these illnesses by a simple conceptual framework.
We need to develop and accept a new paradigm based on the understanding of a viral cause of autoimmunity and indeed MS. Traditional major disease paradigms should be complemented by a new model based on virology and biochemistry.
A highly disruptive course by anti-viral treatment of MS
With the viral causation of autoimmunity, treatment of the disease by anti-viral medication should be a first choice. In fact, the statistics of MS patients that attract HIV and start anti-HIV treatment are very convincing where, a few years after starting with the treatment, the MS just dissolves providing an indication for the fabulous self-regenerating capacity of the human body if the causal factor is removed.
In the field of anti-viral medication, a major breakthrough was achieved a few years ago when the new medicine Letermovir was developed with a completely new working mechanism. When the virus multiply during an infection, its genetic material (DNA) is replicated and packaged into small protein shells, giving rise to newly formed viruses that can proceed to infect other cells. This medicine is thought to block the action of an enzyme of the virus called ‘terminase’, which is involved in packaging the correct length DNA in the protein shells. By blocking the enzyme, the medicine is expected to prevent viruses from reaching maturity, so that no new infectious viruses can be produced.
The medicine shows clear antiviral activity against alpha-, beta-, and gammaherpesviruses and superiority over existing medicine such as val/acyclovir. The new medicine is therefore potentially very promising and “an attractive offer for the effective treatment of additional patients“ including in particular autoimmune diseases of viral origin such as MS. Or, as some would say, it could mean a revolution in immunity and indeed in MS treatment.
I am an MS patient who was trained in a technical discipline. But when I was diagnosed with MS in 2004, I became extremely motivated to unravel the disease that increasingly ruled my life and started to learn more about the disease. In the meanwhile, with my own experiences as an MS patient in mind and with the help of the vast amount of medical literature available on the Internet, some professional advice and the social and patient fora, I have become a semi-literate. The journey has led me to a new understanding of the disease that is presented here. You find more background and literally hundreds of references in the medical literature on this thread.
Paradigm changes often come unexpected and from the outside, and are motivated either by young people who are new to the field or by people who look with fresh eyes at the problem. This has definitely helped me because I did not have to unlearn, my mind was not set by old dogmatic believes that every medical student has to learn if he wants to pass his exams, and I could see new connections and concepts that others perhaps could not see, believe, accept or propose.
A critical need to open the mind set
Autoimmune diseases like Crohn’s Disease and Multiple Sclerosis (MS), in which the immune system attacks its own body rather than predatory invaders, affect 5-20% of the global community. The current scourge of immune diseases points to a growing problem of an overall weakening society. [more on scope of problem, statistics, hits ever younger people] If the trend is not changed, consequences for the general health of our population and that of future generations may be far reaching.
We must spot current trends in societal health, take these trends extremely serious and investigate what is driving them as a matter of urgency. To this end, we should question the status-quo on autoimmunity.
However, as the weight of the status-quo is so immense, every change proposal is at risk to collapse under that weight. Significant systemic problems are pervasive and hamper a course towards investigating or even considering alternative views. The risk is a stagnation while the debate does not get a fair chance and may be dead even before it has started.
In order to find a way out of the impasse, it will be critically necessary that the matter is approached with an open mind, and that alternative views on autoimmunity are explored and new connections investigated with urgency and with force.
The viral connection
The current scourge of immune disease is explained by an immune system that gets ever weaker. There is a multitude of underlying factors: an unhealthy diet, poor quality food (e.g. engrainisation, ‘hardened’ wheat, soil depletion, a lack of flavonoids which generate antioxidants, hydroponic plant growth), a lack of immune system training (e.g. extreme hygiene and indoor/office life, we forgot about fasting which is deep in the Old testament, people who work outdoors are generally much healthier), and stress in a very broad sense. The immune system also weakens with age.
When the immune system weakens, the herpes virus emerges can surface [herpes is a family of viruses]. Most of the human population have it and it has been with us for millions of years, even when we were still apes hanging in the trees of Africa. But all the time it was kept in control by a good functioning immune system. However, the last 50 years, something new is happening that has not been seen before in the history of mankind. Our living conditions have changed so profoundly that the immune system does not keep the virus in check anymore.
The viral tolerance theory - autoimmunity explained
During periods that people are immune compromised (can be the fetal period, the period of the newborn and immune deficient periods), the virus can incorporate some of its genes in the DNA of permissible cells. As such, the virus itself is not programmed to reactivate at specific time intervals but it is the immune system that weakens.
The gene transduction occurs during immune deficiency periods. The incorporated viral genes (transgenes) are tolerant to the body or no immune memory against these transgenes has established.
In MS, in particular the oligodendrocyte precursor cells (OPCs) will be infected. These oligodendrocytic stem cells and their progenitors are preferred by the virus because they differentiate and help replicate the virus. Also for that reason the bone marrow will be infected. Chronic cerebro spinal vascular insufficiency (CCSVI or narrowed internal jugular veins) is a factor – most probably a birth defect - that broke the BBB tissue in an earlier phase. [in rheuma arthritis it is the cartilage of the joints, in MS infection of the cartilage of the sinuses is an issue that helps spreading the virus, for Crohn’s disease permissible cells are in the intestine]
People with transgenes in their body are healthy but predisposed to develop a disease. Predisposed people become diseased when they are infected with a microbe that shares epitodes with the transgenes present in the transgenic cells and will cause an immunological reaction. A chronic low-level EBV infection is suspect in MS but also a Hepatitis vaccinations has been suggested as a trigger. Crohn's disease is associated with measles.
In MS, specific T- and B-cells will pass the CNS and cross-react with the transgenes in the OPCs. Due to this cross-reaction, many OPCs will die which leads to a diminishing number of OPCs, of dendrocytes and a reduced myelination of neurons. EBV resides in the B cell and immortalizes it. So in reaction, the immune system produces more and more. [The count of EBV/Herpes immune cells in my circulation is very high, about 20 x max.]
During this cross-reaction, many mediators will be released by the infiltrating T-cells. This will increase angiogenesis and cause hyperproliferation of surrounding tissue cells in the CNS which in turn causes the pathological lesions (sclerotic plaques) typical for MS.
The symptoms of MS will be mild in relapse-remitting MS but severe in progressive MS depending on the kind of virus that has incorporated part of its genome in the oligodendrocytic stem cells. Inflammatory viruses such as VZV will be associated with mild diseases whereas onco viruses such as EBV will be associated with progressive MS. [I do not exclude the possibility that the VZV mechanism (microbleedings, angiopathy, acute inflammation by blocking of receptors) is followed later on by the EBV mechanism (immortalized B-cells, autoimmunity of transgenic cells) where precisely the kick-in of this latter mechanism explains the second peak in the graph of age of onset of MS. ]
The biochemical reaction hypothesis – the fatigue and brain atrophy explained
Besides the immune reaction against the OPCs, the high load of immune complexes has a second important effect. This is all about fatigue, deterioration of the cell machinery and cellular respiration, disabling glycaldehyde-3 phosphate, the peroxydisation of lipids and other disturbances crucial to the progression of MS but not necessarily major demyelination.
The immune cells have substantial super-oxygen generating capability. The superoxide reacts with the nitric oxide and forms peroxynitrate. The peroxynitrite is by far the worst free radical which causes huge oxidative stress, immune response, jams the gates/mitochondria of the cells, causes effects on the mitochondrial electron transport chain, electron pump inactivation, inhibits ADP to ATP conversion and depletes energy in the form of ATP. And it poisons fat tissue and causes lesions where the brains, biologically seen, are just a lump of fat. I think it also causes what is called herpetic neuralgia where fibromyalgia is not far away.
The lack of energy in MS and other lesions is thus a co-morbidity factor caused by the VZV angiopathy in combination with the EBV high immune complexes. As the number of active gates goes down, we see an increasingly big temperature effect in patients with MS and a loss of muscle strength and sensitivity in the periphery which is an effect possibly as important as the disconnect in the brains. And as cells shrink in size because gates/mitochondria fail, it causes whole brain atrophy. Hence, the typical fatigue, weakening of muscles and whole-brain atrophy observed in MS patients is partly caused by the chronic VZV/EBV infection but with a completely different underlying mechanism than the demyelinating plaques in the brains.
[an extensive analysis of my blood revealed that there are only a few parameters out of their normal margin: that is the high concentration of herpes/EBV immune complexes and high titers of muscles, hence I am eating my own muscles and with that also the connection between nerves and muscles]
In parallel to the MS plaques and immune cell activation in the brain, the NF-KB is triggered by the biochemical cycle mechanism, causing elevated cytokines that contribute to raising the inflammation and Th activity. Where, at some point, mechanisms become all convolved.
A general dysregulation of the metabolism – interlocking vicious cycles
The virus is causal and leads to a general dysregulation of the metabolism.
The problem of disease progression can not be solved by metabolic factors. For sure, hormones are an influence. Hormonal deficiencies often relate to symptoms belonging to lupus, CFS or fibromyalgia or other auto immune diseases. [In my case some hormones were on the low end including cortisol and – as a derived product - testosterone]
At some point in the autoimmune disease process, the HPA axis will be affected causing hormonal deficiencies starting with cortisol. This will have its effects on the gut and further weaken the immune system, thus causing a vicious cycle. [to note: gut problems often precede an MS diagnosis; 90% of the immune system resides in the gut; the role of bacteria in the gut which may help solve autoimmune diseases such as e.g. diabetes T2, the central role of the gastro intestinal tract for good immunity]
While hormones are an influence, administration with hormones (e.g. cortical and DHEA) won’t be convincing. Without tackling the virus and the viral infection, the problem will persist.
This is also true for infection by bacteria and fungi including Borrelia and Cpn, toxoplasmose and such things as toe nail fungus which get their chance when the immune system is fighting the virus [IgG3 depletion]. The infection will aggravate the situation and challenge the immune system further. It is important to get rid of all bacterial infections but fighting the infections alone won’t be enough.
Besides the endocrinological disorders and infectious diseases, there is yet another loop, from the psychological to the physiological. (Short term) stressors that initiate cases of multisystem illnesses act by stimulating nitric oxide synthase (NOS) activity and consequently produce increased levels of nitric oxide and its oxidant product peroxynitrite. Initiation is converted into a chronic illness and a lowered energy metabolism through the activation of vicious cycle mechanisms through which chronic elevation of nitric oxide and peroxynitrite is produced and maintained. All three nitric oxide synthases have been shown to be involved (eNOS, nNOS and iNOS).
The NF-KB is triggered by the biochemical cycle mechanism. The increased NF-KB activity will lead to increased iNOS activity by stimulating through the inflammatory cytokines IL's, TFN and IFN the activity of the iNOS gene itself.
There is a combination of stability and instability, positive and negative feed back loops, leading to what is essentially inflammatory biochemistry. [vicious cycle is the NO/OHNOO hypothesis – Martin Pall]
MS is therefore a subtle multi factorial disease where a number mechanisms and vicious loops are convolved. This explains the erratic course of the disease, and the large variety of symptoms and disease progression seen in MS patients.
Towards to a new paradigm for autoimmune diseases
In our current system for medicare, we see a very large number of overlapping autoimmune diseases with different names. Every expression of a neurological set of symptoms got its own name, based on several types of observations. And we see various signs and symptoms that are overlapping e.g.: slowly progressive symmetric distal sensor motor neuropathy, muscle loss, difficult urine retention, pain worse at night, gender bias, fatigue, distorted Ca levels and inactivated pump mechanisms.
But in fact, a bigger common scheme is underlying. A scheme that encompasses the wide variety of observations, their patterns of case initiation, their chronic nature and many of their shared and unique symptoms and signs of the chronic phase of the disease. A scheme that explains many unexplained observations and the multiple similarities of these illnesses by a simple conceptual framework.
We need to develop and accept a new paradigm based on the understanding of a viral cause of autoimmunity and indeed MS. Traditional major disease paradigms should be complemented by a new model based on virology and biochemistry.
A highly disruptive course by anti-viral treatment of MS
With the viral causation of autoimmunity, treatment of the disease by anti-viral medication should be a first choice. In fact, the statistics of MS patients that attract HIV and start anti-HIV treatment are very convincing where, a few years after starting with the treatment, the MS just dissolves providing an indication for the fabulous self-regenerating capacity of the human body if the causal factor is removed.
In the field of anti-viral medication, a major breakthrough was achieved a few years ago when the new medicine Letermovir was developed with a completely new working mechanism. When the virus multiply during an infection, its genetic material (DNA) is replicated and packaged into small protein shells, giving rise to newly formed viruses that can proceed to infect other cells. This medicine is thought to block the action of an enzyme of the virus called ‘terminase’, which is involved in packaging the correct length DNA in the protein shells. By blocking the enzyme, the medicine is expected to prevent viruses from reaching maturity, so that no new infectious viruses can be produced.
The medicine shows clear antiviral activity against alpha-, beta-, and gammaherpesviruses and superiority over existing medicine such as val/acyclovir. The new medicine is therefore potentially very promising and “an attractive offer for the effective treatment of additional patients“ including in particular autoimmune diseases of viral origin such as MS. Or, as some would say, it could mean a revolution in immunity and indeed in MS treatment.
Re: A new concept and treatment options for MS
Thought you might like this one ...I sure did.
Paradigms in multiple sclerosis: time for a change, time for a unifying concept
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127006/
"...Whilst MS still tightly holds some of its mysteries, light is penetrating the darkness and we are convinced that the time has come when an interdisciplinary programme of research could reduce the current complexity to a simple testable unifying hypothesis and to a rational approach to the development of preventive and therapeutic strategies for this disease..."
Paradigms in multiple sclerosis: time for a change, time for a unifying concept
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127006/
"...Whilst MS still tightly holds some of its mysteries, light is penetrating the darkness and we are convinced that the time has come when an interdisciplinary programme of research could reduce the current complexity to a simple testable unifying hypothesis and to a rational approach to the development of preventive and therapeutic strategies for this disease..."
Re: A new concept and treatment options for MS
Thank you Kronk. These people have got most of the ingredients but they haven't got the recipe. How it all relates together is what you find on this thread.Kronk wrote:Thought you might like this one ...I sure did.
Paradigms in multiple sclerosis: time for a change, time for a unifying concept
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127006/
"...Whilst MS still tightly holds some of its mysteries, light is penetrating the darkness and we are convinced that the time has come when an interdisciplinary programme of research could reduce the current complexity to a simple testable unifying hypothesis and to a rational approach to the development of preventive and therapeutic strategies for this disease..."
Last night I came across this article which has remarkable parallels with my thesis here above (section on the viral connection and the alarming charts in the article). As the fat specialist on this forum, I think you will recognise many of the things said.
http://articles.mercola.com/sites/artic ... sidebanner
Over the last several few weeks, a handful of my professional contacts have encouraged me to carry on with this work but unfortunately none of them wants to be directly associated. See here the current stalemate explained in simple words.
I am afraid that another explanation for the stalemate is by terms like responsibility, accountability and liability. As a consequence, the situation is locked-up completely. The challenge will be to break out of that situation. This is therefore no longer a medical dossier per se.
Re: A new concept and treatment options for MS
Hi Scott,
I just read The Sinatra Solution - Metabolic Cardiology on the cellular machinery. What a beautiful book, almost every page resonates in my mind! Thank you for drawing my attention to this book. I am sure I will return to it many times in the future.
Although the primary focus of the book is the heart, what is said on the failure of the cellular nutrition is completely intermingled with our understanding of MS. If the above posting ‘Towards a revolution in healthcare’ which sets out the viral connection is Chapter 1, then Sinatra’s book on metabolic cardiology would be Chapter 2 of the future Bible on health care. Sinatra’s book should be on the bookshelf of every physician but I am afraid today we are far from that.
I have reconsidered the use of Simvastatin and stopped taking it. I read what Sinatra said. I will take now CoQ10 300mg and other supplementations including Magnesium, from the lists I see come across here, from what Martin Pall suggested and from the recommended lists in the back of Sinatra’s book for fibromyalgia, CFS and Syndrome X. I think that we will need to continue take these supplements for as long as we have the high oxidative stress, that is for as long as the herpes virus reigns our body and is not brought under control by e.g. Letermovir.
I also stopped taking Cortisol/DHEA which is on top of the endocrinological chain with many hormones as derived products. The idea was to improve general health through the endocrine system and the gut function and thus also strengthen the immune system. But here too there may be undesirable side effects and uncertainties.
I will also need to amend my diet and eat more vegetables and less fatty cookies and chocolates. But like yourself, I have difficulty to get control over the kitchen (and my own diet) but I keep trying. I am also considering EPO injections now to increase the red blood cell count and oxygen delivery capacity of the blood and to counter cellular hypoxia and -by Sinatra's insights- free radical build-up. I wonder what you think of that.
Leo
I just read The Sinatra Solution - Metabolic Cardiology on the cellular machinery. What a beautiful book, almost every page resonates in my mind! Thank you for drawing my attention to this book. I am sure I will return to it many times in the future.
Although the primary focus of the book is the heart, what is said on the failure of the cellular nutrition is completely intermingled with our understanding of MS. If the above posting ‘Towards a revolution in healthcare’ which sets out the viral connection is Chapter 1, then Sinatra’s book on metabolic cardiology would be Chapter 2 of the future Bible on health care. Sinatra’s book should be on the bookshelf of every physician but I am afraid today we are far from that.
I have reconsidered the use of Simvastatin and stopped taking it. I read what Sinatra said. I will take now CoQ10 300mg and other supplementations including Magnesium, from the lists I see come across here, from what Martin Pall suggested and from the recommended lists in the back of Sinatra’s book for fibromyalgia, CFS and Syndrome X. I think that we will need to continue take these supplements for as long as we have the high oxidative stress, that is for as long as the herpes virus reigns our body and is not brought under control by e.g. Letermovir.
I also stopped taking Cortisol/DHEA which is on top of the endocrinological chain with many hormones as derived products. The idea was to improve general health through the endocrine system and the gut function and thus also strengthen the immune system. But here too there may be undesirable side effects and uncertainties.
I will also need to amend my diet and eat more vegetables and less fatty cookies and chocolates. But like yourself, I have difficulty to get control over the kitchen (and my own diet) but I keep trying. I am also considering EPO injections now to increase the red blood cell count and oxygen delivery capacity of the blood and to counter cellular hypoxia and -by Sinatra's insights- free radical build-up. I wonder what you think of that.
Leo
Re: A new concept and treatment options for MS
Hi Leo,
I'm glad you got the same sort of buzz I did from reading the book. It would be very interesting to open a dialogue with him. I'm not sure how to from half way round the world. I guess we have to remember he is a cardiologist so he can defer from entering a debate on MS quite justifiably. I find his discussion on the whole formation and recycling of ATP is very clear. In particular he has a bit in the ATP chapter about the ratio of ATP to ADP to AMP which I didn't know about and very good chart (fig 3.10 in my edition) that explains how a decline in the recycling of ADP to ATP ultimately leads to a loss of purines. The consequence of this would be a lower uric acid level which we know exists in MS cohorts. I think the book is very relevant to us.
On free radicals, I not sure. Lowering the build up seems to rely on properly functioning ATP and adequate Q10 to regulate the electron transport chain. Boosting oxygen in the blood might appear to help but if the electrons cannot be captured by Q10 then are those molecules just adding to the oxidative load? I don't know. Buhners explanations on mycoplasmas and bartonellas would also need to be considered as sources of oxidative stress.
Regards
I'm glad you got the same sort of buzz I did from reading the book. It would be very interesting to open a dialogue with him. I'm not sure how to from half way round the world. I guess we have to remember he is a cardiologist so he can defer from entering a debate on MS quite justifiably. I find his discussion on the whole formation and recycling of ATP is very clear. In particular he has a bit in the ATP chapter about the ratio of ATP to ADP to AMP which I didn't know about and very good chart (fig 3.10 in my edition) that explains how a decline in the recycling of ADP to ATP ultimately leads to a loss of purines. The consequence of this would be a lower uric acid level which we know exists in MS cohorts. I think the book is very relevant to us.
On free radicals, I not sure. Lowering the build up seems to rely on properly functioning ATP and adequate Q10 to regulate the electron transport chain. Boosting oxygen in the blood might appear to help but if the electrons cannot be captured by Q10 then are those molecules just adding to the oxidative load? I don't know. Buhners explanations on mycoplasmas and bartonellas would also need to be considered as sources of oxidative stress.
Regards
Re: A new concept and treatment options for MS
Hi Scott,
I fully agree on the need to open dialogue. And it should be global from the outset. A conference where the eminent experts get invited (I think we have a dozen of names) could do the trick. And there are some hopeful signs that some funding could be made available for that (some funding is a necessary prerequisite but it does not have to be millions).
I think we need to unravel the cellular function. Our understanding of the world and in this case the microcosm of our cells is built on concepts. What really happens inside this microcosm is unknown and possibly a lot more complicated – one could certainly say a lot more involved – than the simple concepts we designed and are able to comprehend/apprehend. We may have the main components but then, if I read the Sinatra book, I come across so many variables and interactions, missing links and amazing connections that there are probably one or two other factors that have not been seen or identified so far but that are quite central in this whole machinery.
When unraveling the cellular machinery, I think my cellular failure is caused by gates that don’t function well. They are either too slow to open or they don’t open enough. The fact that I have to pee water 3 times an hour if I eat well (lots of carb) and then start physical exercise (e.g. biking) is an indication that the ‘metabolic pressure of fuel’ is there, probably in abundance, but that the cells don’t take it up fast enough. You could say the cells are not sufficiently sensitive to insulin but probably it is a bit more complicated than that (when I was tested a few years ago, my fasting serum insulin level showed a normal response).
In my family there is no heart failure or other indication of a real mitochondrial failure. My mother's family is big and healthy (my mitochondrial DNA was obtained from my mother). My father's family has the diabetes 2 problem. My brother shows signs of a mitochondrial energy failure but I think that may be gate/transport-function related and not inner-mitochondria related. In other words, the mitochondria are not supplied with enough fuel/oxygen to properly function. In my own case, magnesium helps to aleviate painful legs at night. I relate these symptoms to a (post) herpetic neuralgia and fibromyalgia. Here, MS also affects muscle cells and other peripheral (nerve) cells and is much more than the plaques in the brains. On the role of magnesium, the Sinatra Solution - Metabolic Cardiology says: A magnesium ion is almost always attached to ATP in cells. The magnesium ion reduces the electrochemical charge of ATP, helps ATP move around in the cell, and helps ATP attract various structures in the cells that require energy to function. Suggesting improvement in an impaired transport function.
A further indication may be found in Metformin. Metformin is the widest used drug for diabetes 2 in the world, yet its working mechanism is not known, or not completely understood. If you read the medical literature, it presumably does something with the gates of the cells. Glimperid, another medication for diabetes 2, then gives extra insulin. My father has used these medications for decades. He did well. In his early 60’s, he had this ‘locking’ knee (a sign of ... but he never had MS) that over time completely resolved.
I believe the inner-mitochondrial functioning is ok, but it is the membranes and/or transport function where things get impaired or jammed. And damaging free radical can accumulate. The question is then, what causes the transport problems?
The jamming of the cells is caused by lipid peroxydation (oxidation of fats, including cholesterol and its components). The main problem seems to be the LDL cholesterol. Sinatra calls the oxidation of LDL the pivotal step in the cause of atherosclerosis. In his book, he also refers to the recent discovery of the favorable effect (of CoQ10) on platelets which in my view also points to an impaired gate/membrane function, of insufficiently opening membranes. Both simvastatin and CoQ10 may increase the resistance of LDL to the peroxydation process.
The Vitamin D is involved here as well. Vit D is produced under the skin by cholesterol and sunlight but there is also a forward path where it controls the cholesterol metabolism. Vit D is thus more than just a scavenger of free radicals where its positive effects in MS may be explained by more oxidant resistant cholesterol.
http://articles.mercola.com/sites/artic ... evels.aspx
Is it the platelets aggregation / formation of (micro-) plaques that jam the gates??
http://cardiovascres.oxfordjournals.org ... t/68/3/353
It seems here also lies the source of the endothelial dysfunction
see also http://www.thisisms.com/forum/regimens- ... c6318.html
[the strong temperature effects in PwMS
the Calcium and Na/K ion pumps need more energy than the contraction
fast recovery of motor function when grapes/glucose taken]
We may need to search more on the oxidation of LDL. And perhaps in this same context, I need reconsider the use of simvastatin, in combination with CoQ10, for as long as the viral cause has not been removed.
I'll keep going and will let you know if I find more.
Leo
I fully agree on the need to open dialogue. And it should be global from the outset. A conference where the eminent experts get invited (I think we have a dozen of names) could do the trick. And there are some hopeful signs that some funding could be made available for that (some funding is a necessary prerequisite but it does not have to be millions).
I think we need to unravel the cellular function. Our understanding of the world and in this case the microcosm of our cells is built on concepts. What really happens inside this microcosm is unknown and possibly a lot more complicated – one could certainly say a lot more involved – than the simple concepts we designed and are able to comprehend/apprehend. We may have the main components but then, if I read the Sinatra book, I come across so many variables and interactions, missing links and amazing connections that there are probably one or two other factors that have not been seen or identified so far but that are quite central in this whole machinery.
When unraveling the cellular machinery, I think my cellular failure is caused by gates that don’t function well. They are either too slow to open or they don’t open enough. The fact that I have to pee water 3 times an hour if I eat well (lots of carb) and then start physical exercise (e.g. biking) is an indication that the ‘metabolic pressure of fuel’ is there, probably in abundance, but that the cells don’t take it up fast enough. You could say the cells are not sufficiently sensitive to insulin but probably it is a bit more complicated than that (when I was tested a few years ago, my fasting serum insulin level showed a normal response).
In my family there is no heart failure or other indication of a real mitochondrial failure. My mother's family is big and healthy (my mitochondrial DNA was obtained from my mother). My father's family has the diabetes 2 problem. My brother shows signs of a mitochondrial energy failure but I think that may be gate/transport-function related and not inner-mitochondria related. In other words, the mitochondria are not supplied with enough fuel/oxygen to properly function. In my own case, magnesium helps to aleviate painful legs at night. I relate these symptoms to a (post) herpetic neuralgia and fibromyalgia. Here, MS also affects muscle cells and other peripheral (nerve) cells and is much more than the plaques in the brains. On the role of magnesium, the Sinatra Solution - Metabolic Cardiology says: A magnesium ion is almost always attached to ATP in cells. The magnesium ion reduces the electrochemical charge of ATP, helps ATP move around in the cell, and helps ATP attract various structures in the cells that require energy to function. Suggesting improvement in an impaired transport function.
A further indication may be found in Metformin. Metformin is the widest used drug for diabetes 2 in the world, yet its working mechanism is not known, or not completely understood. If you read the medical literature, it presumably does something with the gates of the cells. Glimperid, another medication for diabetes 2, then gives extra insulin. My father has used these medications for decades. He did well. In his early 60’s, he had this ‘locking’ knee (a sign of ... but he never had MS) that over time completely resolved.
I believe the inner-mitochondrial functioning is ok, but it is the membranes and/or transport function where things get impaired or jammed. And damaging free radical can accumulate. The question is then, what causes the transport problems?
The jamming of the cells is caused by lipid peroxydation (oxidation of fats, including cholesterol and its components). The main problem seems to be the LDL cholesterol. Sinatra calls the oxidation of LDL the pivotal step in the cause of atherosclerosis. In his book, he also refers to the recent discovery of the favorable effect (of CoQ10) on platelets which in my view also points to an impaired gate/membrane function, of insufficiently opening membranes. Both simvastatin and CoQ10 may increase the resistance of LDL to the peroxydation process.
The Vitamin D is involved here as well. Vit D is produced under the skin by cholesterol and sunlight but there is also a forward path where it controls the cholesterol metabolism. Vit D is thus more than just a scavenger of free radicals where its positive effects in MS may be explained by more oxidant resistant cholesterol.
http://articles.mercola.com/sites/artic ... evels.aspx
Is it the platelets aggregation / formation of (micro-) plaques that jam the gates??
http://cardiovascres.oxfordjournals.org ... t/68/3/353
It seems here also lies the source of the endothelial dysfunction
see also http://www.thisisms.com/forum/regimens- ... c6318.html
[the strong temperature effects in PwMS
the Calcium and Na/K ion pumps need more energy than the contraction
fast recovery of motor function when grapes/glucose taken]
We may need to search more on the oxidation of LDL. And perhaps in this same context, I need reconsider the use of simvastatin, in combination with CoQ10, for as long as the viral cause has not been removed.
I'll keep going and will let you know if I find more.
Leo
Last edited by Leonard on Sat Dec 20, 2014 6:07 am, edited 8 times in total.
Re: A new concept and treatment options for MS
Hi Leo,
If you are going down the conference path, I would look to Csaba Szabó. I don't know anything about his biography but his writings are outstanding. Even the stuff from 20 years ago. He may be too old now but his work is still cutting edge on peroxynitrite.
Regards
If you are going down the conference path, I would look to Csaba Szabó. I don't know anything about his biography but his writings are outstanding. Even the stuff from 20 years ago. He may be too old now but his work is still cutting edge on peroxynitrite.
Regards
Re: A new concept and treatment options for MS
Leonard, watching your theory evolve is really impressive. I like that you have not remained steadfastly committed to one theory. You have allowed studies and new research change your thinking, your thread is no longer about CCVSI as it was in the beginning it is much more wide reaching touching on Herpes, Hormones, Bacteria etc. I salute you and hope you continue with this line of thinking. I would caution using Mercola as a reference, every valid piece of info he posts is clouded by 2 pieces of info from a debunked study or other dubious source.
I agree whole-heartedly with your views on Vit D, lipid peroxidation and gate function.
It is interesting that Tecfidera (DMF) a Fumaric Acid Ester is much like vitamin D, formed by the body, in the skin, during exposure to sunlight. What the body uses fumaric acid for isn’t totally clear, it is an intermediate in the KREBs cycle and is normally present in every cell of the body as a component of the citric acid cycle, which is responsible for cellular energy production. However, evidence suggests the people with psoriasis an auto-immune disease may have a biochemical disorder that interferes with the body's ability to produce adequate amounts of fumaric acid. In psoriasis the cellular dysfunction happens at the skin cell, what if MS happens at the immune cell? Same issue different location?
One of the newest research angles into MS is surrounding a 125 year old compound used for leprosy, Clofazimine which happens to target the Potassium Kv1.3 channel. It blocks the channel which prevents a calcium rush into the immune cells. Without enough calcium getting inside a cell, the signaling pathway that turns on the immune response is short-circuited. It is hoped that the combined effect is to shut down a signaling pathway involved in autoimmune disease. Basically this kv1.3 channel may be OVER expressed in MS, a gate that is not functioning correctly?
I have been on the fat angle for quite some time for one reason… there are VERY few constants in MS, but one that I have read in at least 3 studies is that fatty acid profiles in Multiple Sclerosis are skewed from un-saturated fats to saturated fats. In plasma saturated fat adds rigidity to the cell wall, while unsaturated fat makes it more fluid, both are required to form a healthy cell. However too much saturated fat would seal the cell off from interactions with hormones, peptides and others that “program” them. The efficacy of the MS diets can be challenged by asking if the reduction of saturated fat in the diet affects the ratio of them at the cellular level? I would say yes… but I don’t know for sure.
There are sooo many other angles in MS with bacteria, hormones, viruses, etc. etc. but as with any problem there is likely one cause, with the others being symptoms of it. Hopefully science will be able to boil down to that cause and eliminate it.
Personally what I do is attack every possible cause in the hopes that by carpet bombing I hit the pickle barrel. I eat low saturated fat, take mono-ethyl fumarate, Copaxone for the BBB, power lift 4 to 6 days a week at the gym and maintain low bodyfat to increase testosterone, eat several cups of berries a day to increase Valproic Acid, avoid dairy, take Inosine to raise Uric Acid and reduce peroxynitrite-related cellular damage, ALA and Acetyl L Cartinine for free radical control, etc. etc. etc. etc. etc.
I agree whole-heartedly with your views on Vit D, lipid peroxidation and gate function.
It is interesting that Tecfidera (DMF) a Fumaric Acid Ester is much like vitamin D, formed by the body, in the skin, during exposure to sunlight. What the body uses fumaric acid for isn’t totally clear, it is an intermediate in the KREBs cycle and is normally present in every cell of the body as a component of the citric acid cycle, which is responsible for cellular energy production. However, evidence suggests the people with psoriasis an auto-immune disease may have a biochemical disorder that interferes with the body's ability to produce adequate amounts of fumaric acid. In psoriasis the cellular dysfunction happens at the skin cell, what if MS happens at the immune cell? Same issue different location?
One of the newest research angles into MS is surrounding a 125 year old compound used for leprosy, Clofazimine which happens to target the Potassium Kv1.3 channel. It blocks the channel which prevents a calcium rush into the immune cells. Without enough calcium getting inside a cell, the signaling pathway that turns on the immune response is short-circuited. It is hoped that the combined effect is to shut down a signaling pathway involved in autoimmune disease. Basically this kv1.3 channel may be OVER expressed in MS, a gate that is not functioning correctly?
I have been on the fat angle for quite some time for one reason… there are VERY few constants in MS, but one that I have read in at least 3 studies is that fatty acid profiles in Multiple Sclerosis are skewed from un-saturated fats to saturated fats. In plasma saturated fat adds rigidity to the cell wall, while unsaturated fat makes it more fluid, both are required to form a healthy cell. However too much saturated fat would seal the cell off from interactions with hormones, peptides and others that “program” them. The efficacy of the MS diets can be challenged by asking if the reduction of saturated fat in the diet affects the ratio of them at the cellular level? I would say yes… but I don’t know for sure.
There are sooo many other angles in MS with bacteria, hormones, viruses, etc. etc. but as with any problem there is likely one cause, with the others being symptoms of it. Hopefully science will be able to boil down to that cause and eliminate it.
Personally what I do is attack every possible cause in the hopes that by carpet bombing I hit the pickle barrel. I eat low saturated fat, take mono-ethyl fumarate, Copaxone for the BBB, power lift 4 to 6 days a week at the gym and maintain low bodyfat to increase testosterone, eat several cups of berries a day to increase Valproic Acid, avoid dairy, take Inosine to raise Uric Acid and reduce peroxynitrite-related cellular damage, ALA and Acetyl L Cartinine for free radical control, etc. etc. etc. etc. etc.
Re: A new concept and treatment options for MS
Hi Kronk,
Sorry to butt in Leo! I tried dimethyl fumarate (Tecfidera) but went cold on it after the PML issue and how I felt on it.
Where do you find mono-ethyl fumarate and do you have any problems with it?
Regards
Sorry to butt in Leo! I tried dimethyl fumarate (Tecfidera) but went cold on it after the PML issue and how I felt on it.
Where do you find mono-ethyl fumarate and do you have any problems with it?
Regards