Antioxidant drug - future drug for MS?

[Marco]

Researchers at Oregon Health & Science University have discovered that an antioxidant designed more than a dozen years ago to fight damage within human cells significantly helps symptoms in mice that have a multiple sclerosis-like disease.

The antioxidant—called MitoQ—has shown some promise in fighting neurodegenerative diseases. But this is the first time it has been shown to significantly reverse an MS-like disease in an animal.

There is a built-in advantage with MitoQ. Unlike many new drugs, MitoQ has been tested for safety in numerous clinical trails with humans. Since its development in the late 1990s, researchers have tested MitoQ's ability to decrease oxidative damage in mitochondria.

"It appears that MitoQ enters neuronal mitochondria quickly, scavenges free radicals, reduces oxidative insults produced by elevated inflammation, and maintains or even boosts neuronal energy in affected cells," said Reddy.

The hope has been that MitoQ might help treat neurodegenerative diseases like Alzheimer's and Parkinson's. Studies evaluating its helpfulness in treating those diseases are ongoing.

http://medicalxpress.com/news/2013-1...e-disease.html

[Thinkimjob]

Looked up their website, you can get it now for $2 a day, which is cheaper than krill oil. Worth it if it works.

[misslux]

Sounds promising. Thanks for posting!

[knuckle]

For MS newbies and those interested enough in the science...

This stuff sounds like it works like Alpha Lipoic Acid (ALA), which also benefits those little mice with EAE.

ALA is currently in human clinical trial for SPMS at the same place...Oregon Health & Science University

ALA is a heck of a lot cheaper than MitoQ.

Evidently, the participants are taking 1200mg ALA daily.

(I take 600mg ALA daily but it is a sustained release version)

Lipoic Acid for Secondary Progressive Multiple Sclerosis (MS)

http://clinicaltrials.gov/show/NCT01188811

Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis.

http://www.ncbi.nlm.nih.gov/pubmed/14975595

Alpha-lipoic acid (alpha-LA) is a neuroprotective metabolic antioxidant that has been shown to cross the blood brain barrier. We tested whether alpha-LA is capable to prevent MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). Daily oral administration of alpha-LA, starting at the time of immunization, significantly prevented EAE progression as compared to control mice. This was associated with a reduction of CNS infiltrating T cells and macrophages as well as decreased demyelination. We then tested alpha-LA in a therapeutic protocol aimed at suppressing EAE after its onset. Intraperitoneal (i.p.), but not oral, administration of alpha-LA significantly prevented disease progression when compared to vehicle-treated controls. Similarly, we observed significant reduction of demyelination and inflammatory infiltration. This clinical effect was not due to an impairment of MOG35-55 recognition by encephalitogenic T cells. In contrast, MOG-specific T cells showed a decreased production of IFNgamma and IL-4, suggesting an immunosuppressive activity on both Th1 and Th2 cytokines. In addition, alpha-LA inhibited the proteolytic activity of MMP2 and MMP9 only at very high doses. Our data indicate that alpha-LA can effectively interfere with the autoimmune reaction associated with EAE through mechanisms other than its antioxidant activity and supports further studies on the use of alpha-LA as a potential therapy for MS.

And then there's N acetyl glucosamine (NAG) which is also an inexpensive supplement (I take 2000mg daily).

N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis.

http://www.ncbi.nlm.nih.gov/pubmed/21965673

Current treatments and emerging oral therapies for multiple sclerosis (MS) are limited by effectiveness, cost, and/or toxicity. Genetic and environmental factors that alter the branching of Asn (N)-linked glycans result in T cell hyperactivity, promote spontaneous inflammatory demyelination and neurodegeneration in mice, and converge to regulate the risk of MS. The sugar N-acetylglucosamine (GlcNAc) enhances N-glycan branching and inhibits T cell activity and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Here, we report that oral GlcNAc inhibits T-helper 1 (Th1) and T-helper 17 (Th17) responses and attenuates the clinical severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE when administered after disease onset. Oral GlcNAc increased expression of branched N-glycans in T cells in vivo as shown by high pH anion exchange chromatography, MALDI-TOF mass spectroscopy and FACS analysis with the plant lectin l-phytohemagglutinin. Initiating oral GlcNAc treatment on the second day of clinical disease inhibited MOG-induced EAE as well as secretion of interferon-γ, tumor necrosis factor-α, interleukin-17, and interleukin-22. In the more severe 2D2 T cell receptor transgenic EAE model, oral GlcNAc initiated after disease onset also inhibits clinical disease, except for those with rapid lethal progression. These data suggest that oral GlcNAc may provide an inexpensive and nontoxic oral therapeutic agent for MS that directly targets an underlying molecular mechanism causal of disease.

Lastly...Curcumin (from the spice Tumeric)...(I take that too, a supplement)

Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes.

http://www.ncbi.nlm.nih.gov/pubmed/12055272

Experimental allergic encephalomyelitis (EAE) is a CD4(+) Th1 cell-mediated inflammatory demyelinating autoimmune disease of the CNS that serves as an animal model for multiple sclerosis (MS). IL-12 is a proinflammatory cytokine that plays a crucial role in the induction of neural Ag-specific Th1 differentiation and pathogenesis of CNS demyelination in EAE and MS. Curcumin (1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a naturally occurring polyphenolic phytochemical isolated from the rhizome of the medicinal plant Curcuma longa. It has profound anti-inflammatory activity and been traditionally used to treat inflammatory disorders. In this study we have examined the effect and mechanism of action of curcumin on the pathogenesis of CNS demyelination in EAE. In vivo treatment of SJL/J mice with curcumin significantly reduced the duration and clinical severity of active immunization and adoptive transfer EAE. Curcumin inhibited EAE in association with a decrease in IL-12 production from macrophage/microglial cells and differentiation of neural Ag-specific Th1 cells. In vitro treatment of activated T cells with curcumin inhibited IL-12-induced tyrosine phosphorylation of Janus kinase 2, tyrosine kinase 2, and STAT3 and STAT4 transcription factors. The inhibition of Janus kinase-STAT pathway by curcumin resulted in a decrease in IL-12-induced T cell proliferation and Th1 differentiation. These findings highlight the fact that curcumin inhibits EAE by blocking IL-12 signaling in T cells and suggest its use in the treatment of MS and other Th1 cell-mediated inflammatory diseases.

[knuckle]

One other supplement that mice with EAE seem to love...Cinnamon.

There seems to be a connection between spices and MS as regions of the world where spices have traditionally be used in food, such as Southeast Asia, the Middle East and Central America, have very low incidences of MS and other autoimmune diseases. Spices may be neuro-protective.

I wouldn't be at all surprised if you gave mice with EAE a little Cayenne Pepper they would respond well too.

Sodium benzoate, a food additive and a metabolite of cinnamon, modifies T cells at multiple steps and inhibits adoptive transfer of experimental allergic encephalomyelitis.

http://www.ncbi.nlm.nih.gov/pubmed/17579047

Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. This study explores a novel use of sodium benzoate (NaB), a commonly used food additive and a Food and Drug Administration-approved nontoxic drug for urea cycle disorders, in treating the disease process of relapsing-remitting EAE in female SJL/J mice. NaB, administered through drinking water at physiologically tolerable doses, ameliorated clinical symptoms and disease progression of EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice. Histological studies reveal that NaB effectively inhibited infiltration of mononuclear cells and demyelination in the spinal cord of EAE mice. Consequently, NaB also suppressed the expression of proinflammatory molecules and normalized myelin gene expression in the CNS of EAE mice. Furthermore, we observed that NaB switched the differentiation of myelin basic protein-primed T cells from Th1 to Th2 mode, enriched regulatory T cell population, and down-regulated the expression of various contact molecules in T cells. Taken together, our results suggest that NaB modifies encephalitogenic T cells at multiple steps and that NaB may have therapeutic importance in multiple sclerosis.

[ffjosh]

So anyone going to try MITOQ or ALA?

[Cresea]

ALA made my hair thin and fall out.

[Myoak]

The book, Alpha Lipoic Acid Breakthrough by Dr. Burt Berkson is an excellent source of information about ALA. Used copies are often $2 or $3 on Amazon.

Quoting Dr. Berkson… “The The first large human clinical studies using ALA in the United States were carried out by Drs. Fredrick C. Bartter, myself, and associates from the National Institutes of Health (NIH) in the 1970s. We administered ALA to 79 people with severe and acute liver damage at various hospitals around the United States, and 75 recovered full liver function.

Dr. Bartter and I were appointed by the FDA as principal ALA investigators, and I went on to use it successfully for the treatment of chronic liver disease. In combination with low-dose naltrexone, I have used ALA to treat various cancers for which no other treatment exists. (For more information, readers might want to go to PubMed and type in "liver, Berkson.")” End Quote.

I have seen no mention of hair loss in scientific literature or by anyone taking ALA until I read Cresea’s post. I do not doubt his/her word at all but occasionally unrelated things can happen concurrently. For example, after lunch I got a pain in my hip but the sandwich I ate may not have caused it.

I appreciate that you took time to share your experience Cresea and hope I haven’t offended you. Thanks for speaking up my friend, please continue to do so. It is possible more people will speak up if hair loss is indeed a problem with ALA.

Fascinating that ALA is being trialed in MSers. An inexpensive, safe, and effective MS treatment would be a giant leap forward. ALA is readily available, also.

[Cresea]

No offense taken. For 3 months I took ALA for the neuropathy related to my MS. The ALA did help with the tingling in my hands and feet. When I stopped taking the ALA my hair went back to normal. If you do a web search there are other personal accounts from individuals who express that they had the same side effect. I took 600mg daily, and after a month started to notice the loss. I wish it would have just been a sandwich. The ALA was great otherwise.

[Temagami]

I did some reading on mitoQ and my understanding is that coQ10 offers the same chemical, but at a lower concentration and a much lower price. From reading the info, my understanding was that ubiquinone cycles back and forth to ubiquinol so it didn´t seem worth buying the more expensive and more unstable ubiquinol. Correct me if I´m off base please.

[Myoak]

Sorry I don't have the expertise to address your question Temagami; I hope someone else will be able. Best to you.

Cresea, you are refreshing! Have you investigated LDN as a possible treatment for neuropathy related to MS?
I attended a conference presentation made by Dr. Pradeep Chopra a pain management specialist who teaches medicine at Brown University in Chicago last October. He said…

“Almost all chronic pain is neuropathic pain…
“It is not a problem of nerves; it is a problem of cells…
“Gilal cells make up 70-80% of all cells in CNS…
“When gill cells get activated they release cytokines…
“Low Dose Naltrexone reduces pro-inflammatory cytokines…
“Drugs must work on glial not nerves…

Dr. Chopra said that some, not all, of his patients experience a reduction of pain on LDN; some have experienced a sudden and dramatic decrease in pain (overnight) after taking LDN. He spoke of treating CRPS, EDS (connective tissue disorder), and fibromyalgia with LDN. He said most of his fibromyalgia patients start on 1 mg of LDN because they are sensitive to meds.

Although I posted some of this info in another thread Cresea, I wanted to make it available to you specifically. Please don’t overlook the possibility of success with LDN. There are many sources for getting naltrexone if you do not live near a doctor who prescribes it.


Seriously, I hope you will follow up on LDN. Some MSers have great success with it. A trial published in 2008 showed LDN had the effect of slowing MS progression.
http://www.ncbi.nlm.nih.gov/pubmed/18728058
Also, this LDN article may interest you:
http://www.sciencedaily.com/releases...0902133047.htm

[Zuzus11z]

I did some reading on mitoQ and my understanding is that coQ10 offers the same chemical, but at a lower concentration and a much lower price. From reading the info, my understanding was that ubiquinone cycles back and forth to ubiquinol so it didn´t seem worth buying the more expensive and more unstable ubiquinol. Correct me if I´m off base please.

Hi. I don't think you are off base Temegami. I think the proponents of the MitoQ believe it has greater capacity for crossing the BBB. I know some folks who have begun experimenting with MitoQ in the last month and a half. They say they feel more energy and have regained small amounts of functionality. But even they are reluctant to cry out 'miracle'. Not enough time has passed for that to be justifiable.

[Teekybird]

MitoQ

Good thread. I just became aware of MitoQ today, having read an online article titled, "Mitochondria May Play a Role in MS Development and Progression." (Multiple Sclerosis News Today: July 8, 2015).

It definitely sounds promising. Looked it up for purchasing and found it on amazon. According to the reviews there, many are taking it for MS. One interesting comment mentions that it is easy to "mildly overdose" on this, resulting in the exact opposite effect in your body as what you would want it to do. The threshold/amount to 'mildly overdose' would be variable among each individual. Not sure the truth of that statement, but my initial reaction is that it would make sense. While I am very excited at how promising MitoQ sounds, I'm not jumping on the bandwagon just yet. I think I will double my CoQ10 dose and get my Neurologists' opinion MitoQ next time I am in. (Side note: according to amazon, MitoQ is 847 times more effective than CoQ10--not sure of the validity of that statement--nor if doubling my CoQ10 will really matter--but, it is my action plan at the moment).

I'm definitely interested in hearing others' thoughts and experiences related to MitoQ.