Pipeline drug for re-myelination?

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Pipeline drug for re-myelination?

Postby Smilingface » Thu May 15, 2008 5:41 pm

Are there any drugs in the pipeline specifically for re-myelination? I thought a few months ago I saw on this forum one drug that had just been patented but I can't find it now.
Primary Progressive, Onset 10 years ago at age 42, diagnosis 6 years ago, Vit D, Chinese Herbs, Exercise, yoga. So far tried antibiotics, fumaric acid and 4AP. Currently participant in the FTY720/PPMS Trial.<br />
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Postby Frank » Wed May 21, 2008 2:28 pm

Hi Smilingface,

the one you might have in mind was an antibody under development by the Mayo Clinic and Acord Therapeutics.
http://www.thisisms.com/ftopict-4532-re ... l+antibody

Another antibody (as far as I know these are two different) was presented by Biogen Idec:
http://www.thisisms.com/ftopict-4503-re ... l+antibody

'This a link to Acorda Therapeutics R&D pipeline page:
http://www.acorda.com/pipeline_preclinical.asp

An other one to promote new myelin was SYMADEX:
http://www.thisisms.com/ftopict-4846.html

Further more stem cells and some growth factors showed some promise in early animal studies.

Anyway, its important to keep in mind that "just" to be basicly able to build up new myelin might not be sufficient to restore fuctionality to MS patients.
1. The scar tissue along the axons where mylin was damaged, might make it impossible for new mylin to grow around these axons and form new functional isolation.
2. It seems clear that the loss of mylin is only one- and most likely, regarding long term disablility, not the most crucial pathology of MS.

--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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It is worth a try to me for re-myelination

Postby Smilingface » Wed May 21, 2008 6:10 pm

Thanks Frank! You are right, just re-myelinating is not likely enough. In my case, I'll need some of those axons back! Nonetheless, I've recently been trying a herbal extract from an ancient medicinal root called poly gala. Here's some of the supporting research I've found. (I got frustrated thinking about how long the drugs were going to take to get to the market)

1: Neuroscience. 2007 Sep 21;148(4):915-24. Epub 2007 Aug 1.Click here to read Links
Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth.
Naidu M, Kuan CY, Lo WL, Raza M, Tolkovsky A, Mak NK, Wong RN, Keynes R.

Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

We have investigated the neurite growth-stimulating properties of euxanthone, a xanthone derivative isolated from the Chinese medicinal plant Polygala caudata. Euxanthone was shown to exert a marked stimulatory action on neurite outgrowth from chick embryo dorsal root ganglia explanted in collagen gels, in the absence of added neurotrophins. It was also shown to promote cell survival in explanted chick embryo ganglia, and to stimulate neurite outgrowth from isolated adult rat primary sensory neurons in vitro. The further finding that euxanthone stimulates neurite outgrowth from explants of chick embryo retina and ventral spinal cord suggests an action on signaling pathways downstream of neuronal receptors for specific neurotrophic factors. Consistent with this, euxanthone did not promote neurite outgrowth from non-transfected PC12 cells, or from PC12 cells transfected with TrkB or TrkC, under conditions in which these cells extended neurites in response to, respectively, the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3. Western blot analysis of euxanthone-stimulated dorsal root ganglion explants showed that expression of phospho-mitogen-activated protein (MAP) kinase was up-regulated after 1 h of euxanthone-treatment. Inhibition of the MAP kinase pathway using PD98059, a specific inhibitor of MAP kinase kinase, blocked all euxanthone-stimulated neurite outgrowth. However, analysis of phospho-Akt expression indicated that the phosphatidylinositol-3 kinase-Akt pathway, another major signaling pathway engaged by neurotrophins, is not significantly activated by euxanthone. These results suggest that euxanthone promotes neurite outgrowth by selectively activating the MAP kinase pathway.
Primary Progressive, Onset 10 years ago at age 42, diagnosis 6 years ago, Vit D, Chinese Herbs, Exercise, yoga. So far tried antibiotics, fumaric acid and 4AP. Currently participant in the FTY720/PPMS Trial.<br />
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Postby DIM » Thu May 22, 2008 2:23 am

Ok, where can we found xanthones-euxanthones extract from Polygala caudata?
Some more publications:
http://www.springerlink.com/content/a43 ... lltext.pdf
http://www.springerlink.com/content/p3t ... lltext.pdf
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Postby Frank » Thu May 22, 2008 3:20 am

Thanks Similingsface, this is an interesting study!
Did you notice improvements from your poly gala self study?

Regarding the conventional early stage remylination drugs it might be that we dont have to wait that long.
The DMDs have to be trailed for imo at least two years to give a relyable info about their effectivenes, because MS related damage sums up over a long period.
In contrast a remylinating agent could prove to be effective within month (if it acts that fast). So it might realistic to get from the first human trials to the market within less than five years.

One crucial step (that is currently been worked on) is to have some sort of MRI technology that makes remylination visible.

--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Postby DIM » Thu May 22, 2008 10:48 pm

Guess where can we find xanthones except Polygalacea?
Mangostine!
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More on re-myelination with Plant extracts!

Postby Smilingface » Fri May 23, 2008 7:39 pm

Polygala can be found in an herbal extract called Ren Shen Yang Rong Tang (in Chinese) or Ninjn'yoeito (In Japanese). It took me a long time to figure that out! Below is more research on using this plant extract to re-myelinate damaged nerves. I've only been taking it for a week so I don't know if it actually works on humans yet. Stay tuned.....


1: J Neurosci Res. 2007 Apr;85(5):954-66.

Restoration of FcRgamma/Fyn signaling repairs central nervous system
demyelination.

Seiwa C, Yamamoto M, Tanaka K, Fukutake M, Ueki T, Takeda S, Sakai R, Ishige A,
Watanabe K, Akita M, Yagi T, Tanaka K, Asou H.

Department of Neuro-Glia Cell Biology, Tokyo Metropolitan Institute of
Gerontology, Tokyo, Japan.

Disruption of myelin causes severe neurological diseases. An understanding of the mechanisms that control myelination and remyelination is needed to develop therapeutic strategies for demyelinating diseases such as multiple sclerosis
(MS). Our previous finding indicating the critical involvement of the gamma chain of immunogloblin Fc receptors (FcRgamma) and Fyn signaling in oligodendrocyte differentiaion and myelination demands a fundamental revision of the strategies used for MS therapy, because antigen-antibody complexes in MS patients may induce
the direct dysregulation of myelination process as well as the inflammatory destruction of myelin sheath. Here we show that the FcRgamma/Fyn signaling cascade is critically involved in cuprizone-induced demyelination/remyelination,
with no lymphocytic response. The levels of phosphorylated myelin basic proteins (p-MBPs), especially the 21.5-kDa isoform, but not the levels of total MBPs, decreased markedly during demyelination induced by aging, cuprizone treatment, and double knockout of FcRgamma/Fyn genes. We also showed that the recovery from demyelination in cuprizone-treated and aged mice is achieved after administration of the herbal medicine Ninjin'yoeito, an effective therapy targeting the
FcRgamma/Fyn-Rho (Rac1)-MAPK (P38 MAPK)-p-MBPs signaling cascade. These results suggest that the restoration of FcRgamma/Fyn signaling represents a new approach for the treatment of demyelinating diseases.
Primary Progressive, Onset 10 years ago at age 42, diagnosis 6 years ago, Vit D, Chinese Herbs, Exercise, yoga. So far tried antibiotics, fumaric acid and 4AP. Currently participant in the FTY720/PPMS Trial.<br />
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Postby DIM » Sat May 24, 2008 1:58 pm

Would you mind to tell us where can we find this extract?
Thanks anyway for the info!
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Remyelination Herbal Extract

Postby Smilingface » Sat May 24, 2008 3:33 pm

I don't mind one bit. I obtained it from an alternative physician who was not going to give me any information until I showed up as his patient. He spoke to me about 45 minutes about his success with patients using botanical herbs (all Eastern) with auto-immune disease. He told me he had not tried this formula on any MS patients but showed me enough research that I was comfortable enough to become a guinea pig. He charged me $210 and handed me two bottles labeled in Chinese and English --Ren Shen Yang Rong Tang with the words Tianjiang Pharmaceutical CO., LTD, China GMP distributed by Blue Light, INC Ithaca, NY 14850 on them. I've been trying to figure out where I'm going to get my third bottle because I'm not going back to the physician! At a local University is an organic chemist who said he is working on a pure extract of Polygala and it would be ready in 2 months. I did not want to wait the 2 months so went to the alternative physician who already knew I was trying to find a re-myelination herbal formula. That's the story. I should have a conclusion in 4-6 months. Feel free to PM with any other inquiry.
Primary Progressive, Onset 10 years ago at age 42, diagnosis 6 years ago, Vit D, Chinese Herbs, Exercise, yoga. So far tried antibiotics, fumaric acid and 4AP. Currently participant in the FTY720/PPMS Trial.<br />
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Postby DIM » Sun May 25, 2008 1:09 pm

Thank you very much, when the chemist at your local University has the pure polygala extract let me know, I'd like to buy some bottles.

http://alternativehealing.org/ren_shen_ ... g_tang.htm
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Postby DIM » Fri May 30, 2008 4:12 pm

Just for your info I found concetrated Polygalae root (5:1) at 15$/100gr from this site http://www.chinesenaturalherbs.com/.
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Postby Frank » Fri May 30, 2008 4:19 pm

Thanks, nice find! :)

--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Postby gibbledygook » Mon Jun 02, 2008 8:46 am

Hey Smilingface,

I've gone all eastern meds too and have found high dose curcumin and mod dose boswellia to be transformative to my relapsing ms. I am about to try withania somnifera and also rehmannia preparata (so long as chinese quack is agreeable) for their rehabilitory potential. Am also interested in gentiana macrophyllae. These are all either anti-inflammatory or neuronally regenerative. See my last entriesin the regimens section http://www.thisisms.com/ftopic-5261-15.html
:lol:
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Boswellia and curcumin

Postby Smilingface » Mon Jun 02, 2008 3:58 pm

I am taking a proprietary blend that has Boswellia and curcumin in it as well as baicalin, green tea polyphenols --- all designed to reduce inflammation. I started 5 weeks ago. So far so good. I'm glad we are getting some of the same herbs recommended to us by Traditional Chinese Medicine practioners.
That is a good sign!

Now if the polygala actually works for re-myelination, I'll be all set.

I feel much better on this stuff in comparison to CAP but it may not be as effective. We will see ......
Primary Progressive, Onset 10 years ago at age 42, diagnosis 6 years ago, Vit D, Chinese Herbs, Exercise, yoga. So far tried antibiotics, fumaric acid and 4AP. Currently participant in the FTY720/PPMS Trial.<br />
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Postby schnittke » Mon Jun 02, 2008 4:11 pm

Hey Gibbledygook, curious if have an opinion on how the Bio-Curcumin
compares to the regular stuff. Would be nice to take only two of these and
and get 5544 mg.
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