Very Interesting Article on Oxidative Stress and MS......

Discuss Tecfidera (BG-12, dimethyl fumarate) as an oral treatment for multiple sclerosis.

Very Interesting Article on Oxidative Stress and MS......

Postby orion98665 » Tue Sep 18, 2012 6:23 pm

The author of this paper is the same author (Dr. Jack Van Horssen) who found protandim, dietary supplement more effective
than fumurate derivative BG-12.

Conclusions: Our findings indicate that several Nrf2 activators are able to significantly increase antioxidant enzyme production in oligodendrocytes. Interestingly, protandim, a dietary supplement consisting of herbal ingredients, was the most potent inducer and therefore may be the most suited as a therapeutic strategy. Importantly, Nrf2-mediated antioxidant enzyme expression in oligodendrocytes resulted in enhanced oligodendrocyte survival during an oxidative attack.


http://registration.akm.ch/einsicht.php ... KEN_ID=900


Oxidative stress plays a major role in multiple sclerosis (MS), a chronic inflammatory central nervous system (CNS) disease. Invading leukocytes contribute to cell damage and demyelination by producing excessive amounts of cytotoxic mediators, including reactive oxygen species (ROS). To counteract the damaging effects of ROS the CNS is endowed with a repertoire of endogenous antioxidant enzymes, which are regulated by the transcription factor NF-E2-related factor 2 (Nrf2). Upon exposure to ROS, Nrf2 translocates to the nucleus allowing transcriptional activation of various antioxidant enzymes. DJ1 is a protein that is involved in the stabilization of Nrf2 and hence acts as a positive regulator of Nrf2-driven antioxidant protection. Here, we investigate the (sub)cellular localization of Nrf2 and DJ1 in various MS lesion stages and show that Nrf2 is strikingly upregulated in active MS lesions, in both the nucleus and the cytoplasm of infiltrating macrophages and to a lesser extent in reactive astrocytes. Simultaneously, DJ1 protein expression is predominantly increased in astrocytes in both active and chronic inactive MS lesions compared to control brain tissue and normal-appearing white matter. Together, our findings suggest that persistent Nrf2- mediated transcription occurs in active MS lesions, but that this endogenous response is insufficient to prevent ROS-induced cellular damage, which is abundant in inflammatory MS lesions.



http://xa.yimg.com/kq/groups/14113753/5 ... dicine.pdf

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Re: Very Interesting Article on Oxidative Stress and MS.....

Postby milesap » Wed Sep 19, 2012 3:40 am

Protandum was stronger in rat tests, last I looked I'am not a rat (well maybe some people think so). BG12 does a lot more than reduce oxidative stress: its a anti iflammaory, reduces lesions, stops progression better than the crab drugs or gylenia.
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Re: Very Interesting Article on Oxidative Stress and MS.....

Postby NHE » Wed Sep 19, 2012 4:02 am

milesap wrote:Protandum was stronger in rat tests, last I looked I'am not a rat (well maybe some people think so). BG12 does a lot more than reduce oxidative stress: its a anti iflammaory, reduces lesions, stops progression better than the crab drugs or gylenia.


BG12 is a pro-oxidant reactive against thiol groups.
chronic-cerebrospinal-venous-insufficiency-ccsvi-f40/topic19565.html#p188961
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Re: Very Interesting Article on Oxidative Stress and MS.....

Postby cheerleader » Wed Sep 19, 2012 1:49 pm

Milesap-- the mechanism of BG 12 is hypothesized to be an immune modulator....but the honest truth is, no one really knows what it does in vivo in MS in humans, because there are no studies. Of course, that never stops the drug companies.

Oddly enough---BG 12 for MS does not have a specific mechanistic target in the immune system...but that doesn't mean Biogen won't try to find a link and put forth a hypothesis.
Various hypotheses have been advanced for DMF’s mechanism of action, including modulation of the intracellular redox system resulting in consequential effects on nuclear factor kappa B, TNF-alpha, interleukin (IL)-8 and IL-1b. From then, we see effects on anti-inflammatory cytokines such as IL-10 and IL-1RA; decreased expression of adhesion molecules such as ICAM-1, VCAM-1 and E-selectin; stimulation of TH1 and down-regulation of TH2 T-cell subtypes; and induction of apoptosis in antigen-presenting cells and induction in anti-inflammatory stress protein heme oxygenase 1.
But no precise mechanistic target: so is this a deficiency in the regulatory package that Biogen-Idec will submit to the FDA; or if not, how will it address this question?

http://numedicus.co.uk/blog/?p=266

Thanks for sharing the oxidative stress study, Bob....It's a great paper, and the researchers looked at actual brain tissue from autopsied MS brains and found the Nrf2 proteins in lesions. Oxidative stress is a real, verifiable problem in MS, and in cerebral endothelial dysfunction. It's not just some hypothetical.
http://www.ingentaconnect.com/content/m ... 8/art00002
http://www.ccsvi.org/index.php/helping- ... ial-health
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Re: Very Interesting Article on Oxidative Stress and MS.....

Postby Rayboy » Mon Oct 29, 2012 12:53 am

Hello friends,
Last week I contacted PhD Jack Van Horssen, who is the main author of this study led in Amsterdam, asking him if he would advise an empyrical approach on Protandim, in the meantime whil BG12 is approved by the FDA and EMEA (myself living in Spain). Here's his answer. I already ordered my Protandim pack for the next 3 months.

-----------------
Dear Ramon,
Thank your for your mail. As you saw we work with Protandim in the lab and when we treat cells with this mixture we see positive results (cells are better protected against free radicals). However, we have not yet shown that Protandim is also beneficial in an animal model of MS.

Indeed, it seems that Protandim increases antioxidants more pronounced compared to BG12 (again in cell cultures, we don't know whether that is the case in animals and humans), however you need to understand that BG12 works via other pathways as well (immunomodulatory) and we don't have any evidence that Protandim affects the immune system. On the other hand as far as I know there are no real side effects using Protandim so I don't have any claims to not recommend using Protandim as an daily oral supplement. Whether it is really effective is difficult to say as you need large clinical trials and to be honest I don't think that there will be such trials in near future. I wish you and your wife all the best.

Regards, Jack

Jack van Horssen, PhD
Dept of Molecular Cell Biology and Immunology
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Re: Very Interesting Article on Oxidative Stress and MS.....

Postby 1eye » Mon Oct 29, 2012 11:22 am

But aside from Animal Models and Clinical Trials, could be that a combination of the two is better?
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Re: Very Interesting Article on Oxidative Stress and MS.....

Postby Rayboy » Tue Oct 30, 2012 12:59 am

Why combine them, 1eye? They work in the same way concerning neuroprotection-antioxidants enzymes promotion: via the Nrf2 factor. It is true that BG12 has proved effective also as immune-modulator, but then I would not combine it with Protandim, unless it is because Protandim has shown no side effects and is a neutriceutical from natural ingredients.

Myself being an early stage MSer (1 year from Dx, RR form), I have been assigned no DMT yet, and I am (still) only on natural supplements (curcumin, sulforaphane, green tea, D vitamin). Therefore I will give a try to Protandim, which seems to work well on brain cell cultures (from rats but also from humans). The statement from PhD Van Larssen for me is quite explicit, it can do no harm and it may help a lot.
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Re: Very Interesting Article on Oxidative Stress and MS.....

Postby maisiemarie » Sat Dec 01, 2012 8:07 pm

Does anyone know if given intensive nutrition, supplements and the new oral drug if it is possible to turn the illness around. Is it possible to actually implement a program wherein the tissues are being repaired.

Sincerely,
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