Novel Iron Chelators in preclinical models

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Novel Iron Chelators in preclinical models

Postby CureOrBust » Sat Jan 30, 2010 5:14 am

The following passing comment in a financial report caught my interest, but its approaching bed time here.
Novel iron chelators for the treatment of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases and other iron-overload disorders such as thalassaemia and rare anaemias have
been shown in preclinical models to protect cortical neurones and synapses against iron-induced damage. The compounds are in late-stage development candidate selection.

http://www.btgplc.com/PubContent/Docs/BTG%20Interim%20report.Nov2006.pdf
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Postby patientx » Sat Jan 30, 2010 4:58 pm

Very interesting find, Cure.

One interesting thing I saw in this report:

BTG’s licensee Genzyme Corporation reported the results of the 2nd scheduled interim analysis of the Phase II trial of Campath® versus Rebif® in 334 patients with active relapsing-remitting multiple sclerosis. Patients taking Campath® experienced at least a 75% reduction in the risk of relapse after at least two years compared with patients treated with Rebif®.


(So this report is a little old). But i don't quite get the relationship between BTG and Genzyme. What exactly is BTG? Some entity like the Rand Corporation?
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Postby gainsbourg » Tue Feb 02, 2010 1:17 pm

Glad to see more stuff cropping up about chelation, because as everyone has surely now heard - unnatural deposits of free iron are sitting in the brains of all MSrs.

However, I think it is also very important to think about what iron may still be going into the brain as well as thinking of ways of getting it out.

Bear in mind that in Parkinson's Disease, it is known that free iron in the substantia nigra region of the brain, contributes to the gradual destruction of dopamine producing cells.

A study last year (one of the largest and longest running -14 years- prospective studies ever carried out in the connection between diet and illness) showed that there was a massive link between iron in diet and the development of Parkinson's Disease. It showed that those people who ate a diet that included foods that were supplemented with iron were 30% more likely to develop Parkinson's. You can find it here.

Yes, that's right, added iron = 30% increase. The study was so badly worded that it took me some time to decipher these scary findings - and not surprisingly the newspapers have not picked up on it. Eventually I realised that it was free iron supplementation that was the main culprit, because the same study showed that iron compounds included in vitamin supplements had no increased association with the disease (nor did iron which occurs naturally in food, apart from vegetarian sources of iron in those who consumed low levels of vitamin C).

The main source of these unnaturally "fortified" or "enriched" foods was breakfast cereals, followed by bread, rice and pasta. The US and UK governments have insisted on unnaturally adding iron to flour and rice for over 50 years now.

A typical bowl of breakfast cereal will (unnaturally) contribute roughly 50% of your daily iron intake.

Apparently, you can often establish whether free iron is being added to foods like cereal, rice or flour by pouring them into a bowl, then using a large powerful magnet to separate out the iron. I kid you not! Sometimes, far more is added by the machinery than is intended.

I for one will never, ever eat breakfast cereal again, unless it has no added iron, and will be very cautious about eating "enriched" rice, bread, flour, cakes and pasta.

It just shows you what happens when we think we know better than nature. Well meaning governments legislated that iron must be added because so many people were, and still are, deficient in iron.

How "ironic" :cry: is that?


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Postby harry1 » Wed Feb 03, 2010 11:59 am

I've read that Garlic is a natural heavy metal chelator and specifically of Iron and so i thought about taking Garlic powder/capsules etc. as does anyone have any thoughts one way or the other?
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Postby gainsbourg » Wed Feb 03, 2010 2:23 pm

Yes garlic, in fact all cruciferous vegetables (sulphur containing ones like broccoli) are good chelators.

Reading through my last post just now I realise perhaps I should have pointed out that it's only free iron (or loosely bonded iron) that seems to accumulate in neurological illnesses. The reason for this is unknown, though my feeling is it's probably down to the dysmetabolism of iron. As far as I am aware eating a normal or even an iron rich diet isn't a problem. It is iron supplementation in any shape or form that should be avoided at all costs.

There was a lot of stuff in the late 90's about uric acid (UA) levels being very low in people with various neurological disease, including MS, plus an experiment with mice that showed how UA supplememtation enabled mice crippled with the rodent form of MS were able to walk again. Since then there have been all these recent discoveries about iron deposits in MS brains - so was the mice recovery down to the chelating effect of UA?

UA is an antioxidant and also a chelator of free iron. It has been found to work as a preventitive measure against Parkinson's disease.
UA as a chelator in Parkinson's

Glutathione (also a chelator) and UA levels are usually low in MS - maybe this is because the body is using them up to get rid of as much free iron as it can. If this is true then there is now even more reason to get UA and glutathione levels up as high as is safe. UA is a waste product derived from the breakdown the amino acid, purine. You can take it in the form of the supplement iosine but best natural sources of purine are meats, and baked goods with yeast, herring, fish, sardines, mussels, dried beans, lentils, peas, spinach, oatmeal and alcoholic beverages especially beer. Tea should be drunk in moderation.
Glutathione low in MS link

Apparently people with gout (high uric acid) rarely get MS.


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Postby jimmylegs » Wed Feb 03, 2010 3:24 pm

it's when your zinc is not optimal that your uric acid and glutathione levels go down, and iron dysregulation occurs.

some previous posts on this subject

april 18 2009
http://www.thisisms.com/ftopicp-55853-e ... ione#55853
"...anyone else have another guess what handy nutrient elevates your glutathione???"

april 27 2009
http://www.thisisms.com/ftopicp-56317-u ... some#56317
"...all right, some preliminary numbers are in from the lab... URIC ACID is AWESOME. i read some studies that had me thinking the UA status would improve once i dealt with that zinc deficiency. TRUE!"

april 28 2009
http://www.thisisms.com/ftopicp-56380-z ... ione#56380
"...heyas, turns out that zinc elevates not only glutathione, but uric acid -
another great antioxidant that is low in MS cases.
since dx in early '06 my UA was at or below the ms average of 194..."

may 18 2009
http://www.thisisms.com/ftopicp-57772-z ... iron#57772
"...an interesting article, may already be in the mix somewhere, but if not..
http://www.jbc.org/cgi/content/full/283/8/5168
Zinc Deficiency-induced Iron Accumulation...:

jul 24 2009
http://www.thisisms.com/ftopicp-63035-z ... ione#63035
"...when my uric acid was 255, when the zinc result came through it was only 11.6! as of june testing, things are up yet again - zinc to 16.1 (aiming for 18.2) and uric acid to 278 (aiming for 290-300).

sep 12 2009
http://www.thisisms.com/ftopicp-67559-z ... iron#67559
"...zinc status affects iron handling in the body. i've posted on this before here at TIMS..."

sep 16 2009
http://www.thisisms.com/ftopicp-68029-z ... ione#68029
"...just ran across the study quoted below. i figure it belongs with this old liver topic. since i last posted here, i have continued to see good uric acid levels thanks to zinc supplementation, and my d3 absorption appears to have tripled..."

sep 20 2009
http://www.thisisms.com/ftopicp-68425-z ... iron#68425
"http://www.jbc.org/content/283/8/5168.full
Zinc Deficiency-induced Iron Accumulation...
...Treatment of symptomatic heterozygous aceruloplasminemia with oral zinc sulphate...The absence of ceruloplasmin and its ferroxidase activity leads to pathological iron overload in the brain and other organs..."

oct 5 2009
http://www.thisisms.com/ftopicp-70068-z ... iron#70068
"...beating the dead horse some more:
Zinc Deficiency-induced Iron Accumulation..."
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Postby harry1 » Wed Feb 03, 2010 4:31 pm

Gainsbourg

That was interesting about the ''Free'' Iron being a worse problem and also the Uric Acid levels and their connection to MS.

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Postby harry1 » Wed Feb 03, 2010 4:34 pm

Jimmylegs

thanks for posting all the links of earlier discussions about Zinc and it's role as a chelator and i do remember your discussions about that as i went and bought a cal/mag/zinc supplement several weeks back that i take twice daily

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Postby ElMarino » Wed Feb 03, 2010 5:26 pm

Has anyone mentioned Green Tea? If not then I'm mentioning it now..
Apologies for my terrible username. I never thought I'd use the forum much when I registered..
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Postby jimmylegs » Wed Feb 03, 2010 6:05 pm

cool harry, how much zinc is in it?
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Postby jimmylegs » Wed Feb 03, 2010 6:12 pm

elmarino, yes they have

cheer:
oct 30 2009
http://www.thisisms.com/ftopic-8593-day ... cgc-0.html
EGCG, iron and the brain
"...Wanted to make sure all CCSVI stento-teers and CCSVI curious knew about the iron chelating properties of EGCG (green tea extract)- thanks to Sharon for pointing this out again to Ursula-..."

me:
nov 23 2009
http://www.thisisms.com/ftopicp-75912-d ... tion#75912
zinc deficiency is linked to iron dysregulation and deposition.
ms patients are lower in zinc than controls.
average zinc levels in healthy controls, in several different studies, comes out to 18.2 umol/L.

optimizing your zinc levels can have several other benefits including:
- elevating uric acid (by converting toxic ammonia byproducts of digestion)
- apparently helps to increase d3 absorption
- increases intestinal impermeability due to strong tight junctions between cells
- toughens up that blood brain barrier
- can reverse some types of liver damage
- preventative against cancer
- sexy times

the list goes on...

JL
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Postby whyRwehere » Wed Feb 03, 2010 11:31 pm

Thanks for the information everyone...the magnet thing has got me thinking. What happens when people have magnetic therapy....where's the magnet pulling all the iron in their body?
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Postby jimmylegs » Thu Feb 04, 2010 5:24 am

never mind that what about mri lol
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Postby jimmylegs » Thu Feb 04, 2010 6:02 am

harry i hope you caught the relationship between zinc and uric acid and glutathione also, not just the iron thing.

gains, if you take inosine it's one thing, but if your uric acid is low due to a zinc deficiency, all the inosine in the world won't correct that.

further, if you consume high purine foods (which i tried for a couple years with no influence whatever on my ms-average uric acid levels) without adequate zinc, your liver cannot convert amino acid breakdown products to uric acid. all that happens is the ammonia byproduct from which uric acid is made (using zinc) goes up - people with low uric acid can have high levels of ammonia in their system.

The normal process of removing the amino group present on all amino acids produces ammonia. The a -amino group is a catabolic key that protects amino acids from oxidative breakdown. Removing the a -amino group is essential for producing energy from any amino acid.
Under normal circumstances, both the liver and the brain generate ammonia in this removal process, substantially contributing to total body ammonia production. The urea cycle is completed in the liver, where urea is generated from free ammonia.
Overall, activity of the cycle is regulated by the rate of synthesis of N -acetylglutamate (NAG), the enzyme activator that initiates incorporation of ammonia into the cycle. [JL note: i have spent some time looking at how the body does the NAG thing and have found links so far to arginine and vitamin d3 but i don't have a very clear picture yet - also it seems some folks can have a genetic issue with NAG deficiency]
An individual is unlikely to become hyperammonemic unless the conversion system is impaired in some way. In newborns, this impairment is often the result of genetic defects, whereas, in older individuals, the impairment is more often the consequence of a diseased liver.
As ammonia exceeds normal concentration, an increased disturbance of neurotransmission and synthesis of both GABA and glutamine occurs in the CNS. A correlation between arterial ammonia concentration and brain glutamine content in humans has been described. Moreover, brain content of glutamine is correlated with intracranial pressure. In vitro data also suggest that direct glutamine application to astrocytes in culture causes free radical production and induces the membrane permeability transition phenomenon, which leads to ionic gradient dissipation and consequent mitochondrial dysfunction. However, the true mechanism for neurotoxicity of ammonia is not yet completely defined. The pathophysiology of hyperammonemia is that of a CNS toxin that causes irritability, somnolence, vomiting, cerebral edema, and coma that leads to death.

obviously i don't think we're on the verge of coma but there must be a continuum of issues all the way up to fatal cases of hyperammonemia.
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Postby harry1 » Thu Feb 04, 2010 9:37 am

jimmylegs wrote:cool harry, how much zinc is in it?


Hey Jimmy

Sure as i just checked the bottle as it has Calcium 1000 mg, Magnesium 400 mg and Zinc 15 mg as it's just these 3 minerals in the formula.

Is that enough or should i take more Zinc?

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