This Is MS Multiple Sclerosis Community: Knowledge & Support

The abstract below describes another new way of classifying MS. I like it because it blasts EAE right off the top. On the other hand their condemnation of immunosuppression seems too broad to me since there are some successes on that front (campath etc.) Also, their comments about the placebo effect and the existing therapies (CRABs) seems strange. It's repeating an oft-mentioned misunderstanding that they are no better than placebo when they are actually 30% better than placebo in double-blind placebo controlled trials. Anyhow, still interesting...



The sad plight of multiple sclerosis research (low on fact, high on fiction): critical data to support it being a neurocristopathy.


Inflammopharmacology. 2010 Sep 24. [Epub ahead of print]
Behan PO, Chaudhuri A.
Department of Neurology, Institute of Neurological Sciences, Glasgow University, Glasgow, Scotland, UK, pob1w@clinmed.gla.ac.uk.


The literature for evidence of autoimmunity in multiple sclerosis (MS) is analysed critically.

In contrast to the accepted theory, the human counterpart of the animal model experimental autoimmune demyelinating disease, experimental allergic encephalomyelitis (EAE), is not MS but a different demyelinating disorder, i.e. acute disseminated encephalomyelitis and acute haemorrhagic leucoencephalitis. Extrapolation of EAE research to MS has been guided largely by faith and a blind acceptance rather than sound, scientific rationale.

No specific or sensitive immunological test exists that is diagnostic of MS despite the extensive application of modern technology. Immunosuppression has failed to have any consistent effect on prognosis or disease progression. The available data on MS immunotherapy are conflicting, at times contradictory and are based on findings in animals with EAE. They show predominantly a 30% effect in relapsing/remitting MS which suggests powerful placebo effect.

Critical analysis of the epidemiological data shows no association with any specific autoimmune diseases, but does suggest that geographic factors and age at development posit an early onset possibly dependent on environmental influences. Certain neurological diseases are, however, found in association with MS, namely hypertrophic peripheral neuropathy, neurofibromatosis-1, cerebral glioma, glioblastoma multiforme and certain familial forms of narcolepsy. These share a common genetic influence possibly from genes on chromosome 17 affecting cell proliferation. A significant number of these disorders are of neural crest origin, the classical example being abnormalities of the Schwann cell.

These and other data allow us to propose that MS is a developmental neural crest disorder, i.e. a cristopathy, implicating glial cell dysfunction with diffuse blood-brain barrier breakdown. The data on transcription factor SOX10 mutations in animals may explain these bizarre clinical associations with MS and the phenotypic variability of such alterations (Cossais et al. 2010). Research directed to the area of neural crest associations is likely to be rewarding.

http://www.ncbi.nlm.nih.gov/pubmed/20862553

Interesting post dignan. I also found this link to an audio clip that questions old ideas regarding MS.

http://www.abc.net.au/rn/healthreport/s ... 021048.htm

Although it still has an immune response causing the damage it does mention an antigen.

Hi Dignan,
Thanks for posting the article's abstract.



Yes, that's a common misinterpretation of the data. Here's a data plot from Avonex's prescribing information. One should note that the ~30% difference between treatment and placebo is a relative percentage and not an absolute percentage.





NHE

Dr. P.O. Behan had very similar ideas in his Pathogenesis of MS paper a number of years ago. The science and immune system theory just don't add up, yet every single approved MS medication today plays with the patient's immune system.

It's no wonder after 60 years of research that neither a cause nor cure for the disease is available. But one thing is for certain...the drug companies who have provided us with the current medications have raked in billions of dollars and continue to do so.

Harry

The full paper can be found here:
http://www.springerlink.com/content/y35 ... lltext.pdf

As regards the placebo effect the authors seem to accept that the trials should be considered single blinded (e.g due to the side effects).

More on MS as an example of neurocristopathy:



Paradigms in multiple sclerosis: time for a change, time for a unifying concept.

Inflammopharmacology. 2011 May 6. [Epub ahead of print]
Krone B, Grange JM.
Institute of Virology, Centre for Hygiene and Human Genetics, University of Göttingen, Kreuzbergring 57, 37075, Göttingen, Germany.

It has recently been suggested that, rather than being an autoimmune disease, multiple sclerosis (MS) is an example of a neurocristopathy, a pathological process resulting from a faulty development of the neural crest. Whilst several characteristics of the disease suggest a neurocristopathy, other aetiological factors require consideration, including hygiene-related factors that alter the immune responses to common pathogens resulting in an eclipse of immune reactivity that could protect against MS, the possible role of human endogenous retroviruses (HERVs) in pathogenesis and autoimmune phenomena, HLA polymorphism, vitamin D levels before and after birth and immune repair mechanisms.

A postulated aetiological factor in MS, associated with altered vitamin D metabolism and abnormal HERV expression, is a long-lasting disturbed redox regulation in the biosynthesis of a melanoma-like melanin pigment. Although intensive further studies on melanin pigments in nerve tissue in MS are required, the known properties of a pathological form of such pigments in melanoma could explain a number of observations in MS, including the impact of light, UV-light, and vitamin D, and could explain the clinical manifestations of MS on the basis of an oscillating process of oxidative charge and discharge of the pigments and a threshold phenomenon with a change of the quasi-catalytic function of the pigment from destroying reactive oxygen radicals or species to transforming them to more harmful long-persisting highly reactive species.

Taken together with the consequences of an adaptive process in partly demyelinated neurons, resulting in an increase in number of mitochondria, and the impact of stressful life events, these conditions are necessary and sufficient to explain the disease process of MS with its spatial (plaques) and temporal (attacks and remissions) characteristics. This suggested unifying concept of the pathogenesis of MS may open perspectives for prevention, diagnosis and therapy. In particular, prevention may be achieved by vaccinating against Epstein-Barr virus in early childhood.

http://www.ncbi.nlm.nih.gov/pubmed/21547536

I think the line of thought is different. I think the debate is one of pro-nutrition versus anti-inflammation. What do I mean with this?

Take the following example: Metformin (common anti-diabetics drug) activates AMPK (an enzyme that plays a role in cellular energy homeostasis) which in turn stimulates the GLUT (the glucose transporter to the cells). The uptake of glucose / feeding of the cells will improve. In my opinion, the improved nutritional condition will cause a whole chain of reactions. See, eg, http://www.ncbi.nlm.nih.gov/pubmed/19494326 to see what all shows up and presumably is "attenuated" if one takes Metformin.

The believe or the way this is seen is that Metformin has anti-inflammatory properties and suppresses immune responses. But is that really true? I think what actually happens is that the nutritional condition of the cells improves and that because of that many neuro-signaling pathways calm down. See, eg, http://www.ncbi.nlm.nih.gov/pubmed/20865368 which suggest such course of action. The underlying concept is very important here and probably could imply a major breakthrough in the thinking about neuro-inflammatory diseases.

Many of the ideas and suggestions that I have seen pass by on this forum would support such line of thought: a hormonal disbalance in MS with higher cortisol production will over time develop an insulin resistance; the
Vitamin D which plays a role in the glucose absorption and insulin action; the Vitamin D production in relation to the cholesterol and cortisol; the magnesium and the uptake of glucose; zinc that helps bind the insulin and "supports" the adrenal gland, glucolyse processes in the liver, etc.
Many unknowns here, also how it all relates to each other.

The dimension of micro-cellular feeding should be taken into account and may well underly all kinds of neuro-inflammatory expressions as important signalling pathway for the metabolism to signal there is something wrong (that is the undernourished cells). Future therapies should then be designed from the viewpoint to improve nutrition (pro-nutrition) rather than from the viewpoint to suppress or attenuate the inflammation (anti-inflammatory). This would be a very fundamental shift in the thinking, perhaps even needs a complete rewrite of the medical doctrine.

For further information in the low glocuse concept see http://www.thisisms.com/ftopict-15188.html

And, of course, increased glucose levels will require increased oxygen supply and working mitochondria so that it can effectively be converted to ATP (energy!). If there is no oxygen you will end up with ineffective glucose utilization, very low amounts of produced ATP and anaerobic metabolism byproducts.

_________________
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."

very true...

I see the mitochondria as the engine. CoQ10 and Vitamin B supplementation as the oil to ensure the engine runs smoothly. The glucose equals the fuel that of course needs the oxygen from the air to react and give the power boost.

Unless the lactate is used but that also requires oxygen.

Unfortunately, there is lack of oxygen in the MS brain and the mitochondria suffer from DNA deletions. This is what makes me think that glucose by itself is not enough.

_________________
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."

Talking of DNA deletions, this is very interesting.
It of course comes from the "iron" side, but ties up the chain reactions.
Enjoy (it references to Zamboni and all the usuals)
Cheers..........

http://dbkgroup.org/Papers/kell_irondd_at10.pdf