Theoretical Immunology

[jimmylegs]

"Idebenone is a synthetic analog of one of life's most essential biochemicals, coenzyme Q10."

[Leonard]

A promising spin off of CO-Q-10 is idebenone, which is supposedly a much more potent CO-Q-10 synthesys. It's actually in trials for PPMS.

whow amazing, any references there?

http://clinicaltrials.gov/ct2/show/NCT0 ... 248&rank=1

Idebenone is available at several on line vitamin shops.

It seems the trial is ongoing for 2 years with 80 participants.
Any chance of being able to obtain intermediate results?

[Leonard]

From http://en.wikipedia.org/wiki/Coenzyme_Q

CoQ10 and electron transport chain

CoQ10, fat-soluble and therefore mobile in cellular membranes, plays a unique role in the electron transport chain (ETC). In the inner mitochondrial membrane electrons from NADH and succinate pass through the ETC to the oxygen, which is then reduced to water. The transfer of electrons through ETC results in the pumping of H+ across the membrane creating a proton gradient across the membrane, which is used by ATP synthase (located on the membrane) to generate ATP. CoQ10 functions as an electron carrier from enzyme complex I and enzyme complex II to complex III in this process. This is crucial in the process, since no other molecule can perform this function. Thus, CoQ10 functions in every cell of the body to synthesize energy.

My assessment:
The Na/K pump necessary for our motor functions works by the ATPase, see my posting of 20 March 2011 9:21am. If there is insufficient energy, sodium will move into the cell and calcium out of the cell. Perhaps the mechanism that puts things in motion is on the inner cell membrane where the H+ is pumped across the membrane and CoQ10 is the essential transport vehicle.

I am not a micro-cellular specialist. But I feel the inner and outer membrane, the ETC and the Na/K/Ca pump are all electrically linked together in some way. Any views?


http://en.wikipedia.org/wiki/Idebenone#cite_note-13

[Algis]

For what it worth; I have been taking CoQ10 6 months with no noticeable difference (positive or negative).
I stopped because it is not cost-effective.

[gainsbourg]

Idebenone is a form of coenzyme Q(10) with potent antioxidant properties – a free radical scavenger. There is an iron connection here because idebenone has been successfully used in the treatment of Friereich's Ataxia - a rare disease caused by a defective gene which causes faulty iron metabolism. Friedreich's has many symptoms common to MS so it is no wonder they are using it to treat MS.


gainsbourg

[jimmylegs]

yes, a synthetic analog form.

as to iron, i have posted frequently on insufficient zinc in ms patients with implications for iron dysregulation and deposition.

here are two abstracts on freidrich's ataxia and zinc. interesting...

Zinc and taurine in Friedreich's ataxia.
http://www.ncbi.nlm.nih.gov/pubmed/6509414

Zinc and taurine were measured in urine in the fasting state and following a 4mg/kg load of taurine in subjects with Friedreich's Ataxia (FA), and healthy controls (C), and subjects with Duchenne type muscular dystrophy (MD). Of the FA, 25% had increased fasting excretion of zinc, and 50% had increased excretion of zinc following the taurine load. ... As an index of zinc deficiency, uptake of zinc by erythrocytes was measured in all subjects and in heterozygotes for FA. The pattern of uptake was abnormal for FA and heterozygotes. Hair analysis for zinc showed that 10 of the 12 FA subjects had low values

... i bet if i could get my hands on full text i would disagree with their assessment of how many FA patients had low values. my access only goes back to the 90s for this journal

Zinc suppresses the iron-accumulation phenotype of Saccharomyces cerevisiae lacking the yeast frataxin homologue (Yfh1)
http://www.ncbi.nlm.nih.gov/pmc/article ... 868958.pdf

...Excess zinc in the growth medium also influenced the phenotypes of yfh1 cells. It prevented the accumulation of iron in the mitochondria of yfh1 cells and increased the growth rate of these cells and their resistance to oxidative stress. However, zinc did not restore the deficiency of Fe–S and haem proteins of yfh1 cells. Zinc inhibited mitochondrial respiration and protected Yah1p, the mitochondrial ferredoxin. These results suggest that zinc nutrition may be important in the aetiology of Friedreich’s ataxia

[gainsbourg]

I agree that zinc is of paramount importance in MS bcause it is so often deficient - even though very likely your neurolgist will never so much as mention the word zinc.

Friedreich’s is caused by an iron accumulation in the mitochondria of nerve cells due to a rare genetic flaw which causes faulty iron metabolism. I have been convinced for a while that incorrect iron metabolism is also happening in MS and is the likely cause of the mystery iron deposits.

Of course MS could be causing the faulty iron metabolism rather than the other way round. This argument can also be used to counter any theory of MS that points at metabolism.

High doses of zinc will tend to reduce the absorption of iron (magnesium, Vitamin B2 and E are also iron antagonists)

[jimmylegs]

!!!!! banging head against wall

[jimmylegs]

http://www.ninds.nih.gov/disorders/frie ... ataxia.htm
Friedreich’s ataxia is caused by a defect (mutation) in a gene labeled FXN.

http://ghr.nlm.nih.gov/gene/FXN
The FXN gene provides instructions for making a protein called frataxin. This protein is found in cells throughout the body, with the highest levels in the heart, spinal cord, liver, pancreas, and muscles used for voluntary movement (skeletal muscles). Within cells, frataxin is found in energy-producing structures called mitochondria. Although its function is not fully understood, frataxin appears to help assemble clusters of iron and sulfur molecules that are critical for the function of many proteins, including those needed for energy production.

Expression of Human Frataxin Is Regulated by Transcription Factors SRF and TFAP2
http://www.plosone.org/article/info:doi ... ne.0012286

Cardiac tissue enriched factors serum response factor (SRF) and GATA-4 are mutual coregulators.
http://www.ncbi.nlm.nih.gov/pubmed/11003651
"...serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts..."

Cardiac abnormalities induced by zinc deficiency are associated with alterations in the expression of genes regulated by the zinc-finger transcription factor GATA-4.
http://www.experts.scival.com/ucdavis/p ... n&u_id=254

[Leonard]

I agree that zinc is of paramount importance in MS bcause it is so often deficient - even though very likely your neurolgist will never so much as mention the word zinc.

Friedreich’s is caused by an iron accumulation in the mitochondria of nerve cells due to a rare genetic flaw which causes faulty iron metabolism. I have been convinced for a while that incorrect iron metabolism is also happening in MS and is the likely cause of the mystery iron deposits.

Of course MS could be causing the faulty iron metabolism rather than the other way round. This argument can also be used to counter any theory of MS that points at metabolism.

High doses of zinc will tend to reduce the absorption of iron (magnesium, Vitamin B2 and E are also iron antagonists)

Iron deposits are a perfectly normal phenomenon if the drainage is impaired, for any organ or limbs. It was the very first thing that a vascular doctor told me 1,5 year ago when I had first heard about ccsvi.

It would not be entirely illogical if the mitochondria of nerve cells would accummulate iron after many years of iron loading in the nearby veins that are just Angstroms apart.

I guess a high iron load of the mitochondria is not good for their proper functioning. Are there any data?
High doses of zinc will tend to reduce the absorption of iron; magnesium, Vitamin B2 and E are also iron antagonists. Any data?
Suppose the mitochondria of our nerve cells is iron-loaded, is there anything we could do to normalise the situation?

[Leonard]

I invite you to look at this wiki page. The page seems to be kept up to date.
http://en.wikipedia.org/wiki/Chronic_ce ... ufficiency
quote: Consequences of Proposed CCSVI syndrome include intracranial hypoxia, delayed perfusion, reduced drainage or catabolites, Increased transmural pressure, [11] and iron deposits around the cerebral veins. [12] [13] Multiple sclerosis Has Been Proposed As The main outcome or CCSVI.

Hypoxia is mentioned but strangely enough there is absolutely no mention of low glucose as a possible cause or even a link to the glucose condition.
Therefore, is the current debate on ccsvi as the cause of MS a false debate? Is the low glucose condition consciously kept outside the debate, at least the debate that we see, while here is precisely the real issue?

This recent link points to a message from a New York neurologist who seems to believe in a glucose link: http://www.ccsvi.mx/fatigue-ms-ccsvi
quote For example, fluctuations in the supply or metabolism of glucose, the primary fuel for the brain, may have some impact on declines ..

This doctor argues: " .. have the neurologists considered the physics of fluid dynamics on the complex bio-chemical interactions that they discuss in their research papers? If so, what was the result? If not, why not?
.. neurologists .. have .. held the field for the last 25 years and it is conceivable that their current scientific background alone is not sufficiently complete to come up with a complete solution."
http://liberationtreatmentccsvi.com/201 ... liberated/

A Google search on hypoglycaemia and MS delivered this fascinating link: Insulin counter-regulation in multiple sclerosis
http://www.ncbi.nlm.nih.gov/pubmed/2291833
Clearly there must be massive uploading of this document as Google pushes it forward.
I recognise a number of things in it for myself.
I will look into it further but your views would be most welcome.

[gainsbourg]

Leonard said:

is there anything we could do to normalise the (iron) situation?

Now there's a good question! Keep zinc and all essential nutrients up for a start.

I have an unorthodox view about what causes MS and believe that the many varietes of herpes which have strong associations with the disease (they are in the nerve ganglia of everyone with MS) play a causal role. I think that herpes somehow scares the immune system into unnecessary autoimmune action by its mere presence, and this in turn disrupts iron metabolism and causes the iron deposits.

So many nerological diseases are associated with excess iron in the brain, Parkinson's; Alzheimers for example - it would be much too simplistic to say they are all caused by venous problems. When we experience stress (i.e. modern, western civilised life) we place a heavy demand on the white matter of the CNS. I believe this strain somehow stimulates herpes which in turn triggers the immune system into unnecessary action in certain unlucky individuals. Yes it could be a metabolic flaw that develops, because this chronic, unnatural, increased demand on nerves places an increased demand for nurients like glucose and oxygen - which nerves need in order to work.

Bear in mind that both herpes outbreaks and MS attacks have strong associations with stress. Mine is an unusual theory I know! But then your theory, Leonard, isn't exactly orthodox!


gainsbourg

[Leonard]

Bear in mind that both herpes outbreaks and MS attacks have strong associations with stress. Mine is an unusual theory I know! But then your theory, Leonard, isn't exactly orthodox!
gainsbourg

@gainsbourg: your theory is not so unusual. On page 4 of this thread, there is mention of the need for the presence of a virus (eg Bar Eppstein) to start the inflammation process. I suppose this could also be the herpes virus. These virusses find fertile ground because of the malnutrition.

On my own theory and the subject of this thread: I think it is orthodox, very orthodox, perhaps even so orthodox that specialists and researchers from around the world have overlooked it!

What I find unorthodox is the fact that we as amateurs generate content that unveils the secrets of MS. What I find unorthodox is that the medical world does not seem to pick up the dimension of nutrition and seems to be wasting its energy in the fight of vascular versus auto-immunity. What I find unorthodox is that the (inbalance of the) metabolism is consistently ignored or neglected. Still the evidences accummulate.. (recent Danish research on the thyriod gland and MS just reported).

Clearly, we are standing here at the eve of a revolution, a new age, where with the help of the social fora, the search engines and the Internet, new forms of "creative, transformative or derivative works" become possible that favour innovative uses of works and stimulate the production of added value User Generated Content. And I believe we have just seen the pre-face of this new era.

[Bethr]

Great thread. Keep it up and we'll have it figured out by next year
My choice is to not take any supplements for now. Of course, this is because I found such relief from reducing levels of iron in my body, and the results were outstanding. If I take zinc, I don't feel so good.

So I've decided not to throw fuel on the fire, and just keep working on maintaining my iron levels to stay well.

With the body mishandling minerals in the body, I'd rather not complicate it by taking anything, I just eat well. I've posted elswhere how when iron overload is treated (iron reduced), zinc levels come up on their own, so I'll stick with that for now. This is very individual to me, but may help in the puzzle.

In class type 1 iron overloading zinc collects in the liver and spleen, along with the iron. Low zinc levels are seen on tests. Firing more zinc into your body in that situation to try to counteract this seems dangerous, as the body is obviously not metabolising it well and storing it in dangerous places.
That's the backbone of my theory for those of us with iron loading genes.
If you have a classic type 1 iron overloading gene, MS will progress faster.
It's been researched.

[jimmylegs]

yeah no. absolutely and of course, folks with hemochromatosis need to make different decisions about mineral supplementation than people that don't.