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Conference: Molecular Basis of Clinical Medicine
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Prof Trevor Marshall
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 Posted: Sun Jun 24th, 2012 06:47

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The video of my presentation is at: http://youtu.be/_rFmAMDdbjs

Note particularly that at 29:20 I discuss, for the first time in public, how many of the 'SNPs' detected as Genetic SNPs and mutations, may actually be software errors resulting from the presence of microbial DNA in the human blood and tissue samples used in that research. Amy has previously covered this issue in our Metagenomics book chapter, but now I feel it is time to start publicly pointing out that 'the emperor has no clothes'. Or few clothes, as the case may be...

This was an excellent conference, and I was very impressed both with the scientific understanding of the Russian luminaries, and their objective evaluation of the 'failures' of current medical practice. I felt among friends, and indeed made many friendships which I hope will be long-lasting.

One of the invited speakers was Shimon Slavin, from CTCI, the Center for Cell Therapy and Cancer Immunotherapy, in Tel Aviv. Shimon has been using stem cells to treat human disease for at least a decade. He extracts mesenchymal stem cells from a patient's bone marrow, cultures them to grow several thousand times in number, and then injects them back into the body. When specific organs need repair, he uses an ultrasound 'acoustic funnel' to coax them to the regions where they will do the most good.

There are some videos on YouTube describing his work:
http://www.youtube.com/watch?v=pq4c6sq43Z0

He emphasized during his presentation that the exceptional cases, like the one in this video below, are "very, very, few" (his exact words)
http://www.youtube.com/watch?v=5hAVAANfhY0

Further, as he says in his first video, the best results are achieved with early stage disease. I liked that honesty. Indeed, what he told me, both privately and in his presentation, fitted perfectly with our own pathogenesis. Here is a summary.

First, stem cells are not a cure. Treatments are often required on an ongoing basis. Further, he has found it helpful to "kill off the unfriendly T-Cells" before putting back the fresh Mesenchymal stem cells. These stem cells are capable of differentiating to hematopoetic, and therefore to monocytes, macrophages and lymphocytes.

No immune suppression is needed, the stem cells are cultured from the patient, and the patient does not reject them.

I will follow-up our initial discussions with Shimon, as I think there may well be a way of integrating his short-term approach with our longer-term focus.

A word of caution here. There are many charlatans advertising stem-cell therapies on the Internet, and many reputable research centers trying to get a start in Stem Cell technologies. It is important to understand the success rate of anything you read about, and double-check it against a large number of known testimonials. For example, I could find no follow-up posts saying that this patient's therapy was a success, or that the clinic advertising that therapy had any useful rate of success. Stem cell transplantation and regeneration is still at a very early stage, with a near-zero rate of true success.

I am bringing up the topic for discussion here so that you can look at the experience of a clinic, and of Dr Slavin, who treats Film Stars, Politicians, and world leaders, and who has been doing so for many years.

I do see some promise, and I will follow that up aggressively :)
 
..Trevor..
 

ChrisMavo
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 Posted: Sun Jun 24th, 2012 12:47

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Another great presentation Dr Marshall! 

I especially appreciate your explanation of the current state of affairs regarding stem cell therapy.  In the future, stem cell treatment may well be a complimentary treatment along with the MP.  Perhaps once the immune system has been restored and cleaned up of the microbiota, stem cell therapy could speed healing.   This may well be helpful for neurodegenerative diseases like MS and ALS! 

As you know, my neurologist has mentioned a local stem cell study for ALS starting sometime in 2013 and wanted to know if I am interested in being in it.  I think they are using a different kind of stem cells that may require immune suppression.  So, I do not know if I would opt for it.   By that time I would be well over 3 years on the MP.  With a much more healthy immune system the stem cell therapy could speed my recovery and be permanent! 

Thanks for all you do for all of us!

Good health!
Chris :D



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Prof Trevor Marshall
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 Posted: Sun Jun 24th, 2012 12:57

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Chris, all stem cell therapy is not the same. I can show you clinics whose results have been dismal. You want to make sure you are only associated with a clinic that has a track record for good results. You really have no room for any margin of error. It is important to choose the correct opportunities, and I doubt they will come in 2013, because 'proof-of-concept' of 'cure' is nowhere close in 2012, even for CTCI.
 

ChrisMavo
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 Posted: Sun Jun 24th, 2012 13:06

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Thanks Dr Marshall.  I certainly have not made any decisions regarding stem cell therapies at this time.  I too realize that the current state of affairs in stem cell therapy is nothing more than discovery and experimentation with very few success stories.  My decision will be guided by where I am at in recovery by that time. And, rest assured, anything I decide would be after thorough consultation with you first!



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Prof Trevor Marshall
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 Posted: Sun Jun 24th, 2012 13:09

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2013 is when the Moscow preventative disease effort is scheduled to get under way. I assume we will be participants, and I assume CTCI will. So, even if not before Moscow starts up, I would expect to see very close collaboration at that point :)
 

Russ
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 Posted: Sun Jun 24th, 2012 13:13

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Thanks for the conference presentation Dr. Marshall and for the info on stem cells.  What do you see as the main benefit that stem cell therapy in combination with the MP could provide?  Faster recovery?  Less IP?  Deeper healing?  Healing of things like fibrosis that the MP seems to address very slowly, if at all?  Thanks.

Prof Trevor Marshall
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 Posted: Sun Jun 24th, 2012 13:24

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Fibrotic tissue is already in place. It has to be resorbed, and stem cells aren't going to help that too much I fear.

Mesenchymal stem cells can differentiate into monocytes and macrophages, and help replenish them, at the same time as building new tissues. Exactly what they do best is still to be explored, I think, as the researchers in that field have found long-term recovery beyond their grasp. We need to merge the MP long-term understanding (that the new stem cells will become infected) with their ability to generate short-term improvement (via stem cells). I think that would provide a very flexible therapeutic approach.

With many people, it takes a long time for the MP to start showing tangible benefits, while for stem cells the initial tangible benefits are quickly lost, as time goes by. The potential for synergy seems pretty clear, I think :) Especially as no immunosuppression is needed with the mesenchymal approach.
 

Russ
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 Posted: Sun Jun 24th, 2012 13:40

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Sounds good.  Sign me up!

ChrisMavo
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 Posted: Sun Jun 24th, 2012 15:28

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Dr Trevor Marshall wro
With many people, it takes a long time for the MP to start showing tangible benefits, while for stem cells the initial tangible benefits are quickly lost, as time goes by. The potential for synergy seems pretty clear, I think :) Especially as no immunosuppression is needed with the mesenchymal approach.
 

I have thought the same exact thing for two years now!  :)



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Nick B.
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 Posted: Sun Jun 24th, 2012 21:21

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Just a quick note that at approx 32:24 into the above talk, by Dr Marshall, there is a reference to the TheSeed from Argonne National Labs, on the second to last slide.     this can now be found at: 

http://theseed.org/wiki/Home_of_the_SEED

Nick B  :)



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Prof Trevor Marshall
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 Posted: Sun Jun 24th, 2012 21:25

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Nick,
My URL should have been http://www.TheSeed.org
Ooops...
 

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 Posted: Mon Jun 25th, 2012 10:35

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Sounds like a ray of hope for people with type 1 diabetes who have been on the MP for a while (like me). Also gives me hope that someday the hearing in my right ear could be restored.

Thank you.



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wrotek
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 Posted: Tue Jun 26th, 2012 05:22

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"Microbiome makes us genetically unique"  that is an interesting statement.

Perhaps this can influence different reaction of people to different types of diets ?

What about Mycobacterium Leprae, does it knock out VDR ?

Last edited on Tue Jun 26th, 2012 05:24 by wrotek



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Prof Trevor Marshall
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 Posted: Tue Jun 26th, 2012 05:26

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Yes, it is a provocative statement Wrotek, and it has to be looked at in the light of my final slide, on how software errors from the microbes corrupt the human SNP database...

Everybody's GI flora will be a little bit different, and the flora balance changes after severe infection. Antibiotics can change the flora profoundly, some wiping it out for months (Dave Relman gave a talk about this at Seattle recently).

I have no data on M.leprae and VDR...
 
 

Last edited on Tue Jun 26th, 2012 05:33 by Prof Trevor Marshall

wrotek
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 Posted: Tue Jun 26th, 2012 06:04

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Perhaps this paper about M. Leprae is of some use , i just found it.

http://www.ncbi.nlm.nih.gov/pubmed/22286305


MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy.


Liu PT, Wheelwright M, Teles R, Komisopoulou E, Edfeldt K, Ferguson B, Mehta MD, Vazirnia A, Rea TH, Sarno EN, Graeber TG, Modlin RL.

SourceOrthopaedic Hospital Research Center, University of California-Los Angeles, Los Angeles, California, USA. ptliu@mednet.ucla.edu

Abstract Leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a spectrum of clinical presentations that correlate with host immune responses. Here we identified 13 miRNAs that were differentially expressed in the lesions of subjects with progressive lepromatous (L-lep) versus the self-limited tuberculoid (T-lep) disease. Bioinformatic analysis revealed a significant enrichment of L-lep-specific miRNAs that preferentially target key immune genes downregulated in L-lep versus T-lep lesions. The most differentially expressed miRNA in L-lep lesions, hsa-mir-21, was upregulated in Mycobacterium leprae-infected monocytes. By directly downregulating Toll-like receptor 2/1 heterodimer (TLR2/1)-induced CYP27B1 and IL1B expression as well as indirectly upregulating interleukin-10 (IL-10), hsa-mir-21 inhibited expression of the genes encoding two vitamin D-dependent antimicrobial peptides, CAMP and DEFB4A. Conversely, knockdown of hsa-mir-21 in M. leprae-infected monocytes enhanced expression of CAMP and DEFB4A and restored TLR2/1-mediated antimicrobial activity against M. leprae. Therefore, the ability of M. leprae to upregulate hsa-mir-21 targets multiple genes associated with the immunologically localized disease form, providing an effective mechanism to escape from the vitamin D-dependent antimicrobial pathway.
Also
http://www.ncbi.nlm.nih.gov/pubmed/20887706
Low serum levels of cathelicidin LL-37 in leprosy.

Abstract The antimicrobial peptide cathelicidin LL-37 possesses antituberculous activity, its association with other mycobacterial diseases, such as leprosy, is unknown. We studied serum cathelicidin and 25OH-vitamin D3 levels in 29 leprosy patients and 19 healthy individuals from Yemen. Cathelicidin levels were significantly lower in both treated (n=15) and untreated leprosy patients (n=14) when compared to controls (P<0.001). Within leprosy patients, levels were lower in those who very recently developed disease (untreated group) when compared to already treated patients (P<0.05). 25OH-vitamin D3 levels were not different between groups. The results suggest a potential association of cathelicidin LL-37 with Mycobacterium leprae infection. Copyright © 2010 Elsevier B.V. All rights reserved.

Last edited on Tue Jun 26th, 2012 06:16 by wrotek



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leroybrown
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 Posted: Tue Jun 26th, 2012 06:38

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I'm curious. How do they kill off the unfriendly T cells? The wikipedia article claims that mesenchymal stem cells do not become hematopoetic cells, but I guess he has found that they do? How do they collect the stem cells? Do they use growth factors?

If your disease is from infection, wouldn't the stem cells be infected too?

Stem cell therapies are available at a great price for tendon injuries in horses, but I don't know how well they are supposed to work.

I have also met with the transplant clinic at the hospital and none of the bone marrow transplant process would be anything I'd want to do.

Thanks,
Deb



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And I don't know when - Kate Bush
Aplastic anemia Apr/10, PRCA Jan/09, Agranulocytosis 1991
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Prof Trevor Marshall
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 Posted: Tue Jun 26th, 2012 10:06

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Deb,
Shimon uses a patients own cells. Extracts them, grows them, and then injects them. No rejection that way. No immunosupressants.

I don't think he had a clear picture himself of how he "killed off the bad cells" but that was what he said in his presentation :) Stem cell science is still at a very early stage, especially when compared with the MP :) The success rate they get is a lot lower, too :)

He was emphatic that his stem cells replenished the immune system cells.


leroybrown
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 Posted: Tue Jun 26th, 2012 10:21

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When they do autologous stem cell transplants at the hospital (using your own cells) they first kill off your bone marrow with chemo and/or radiation. They also give you growth factors (neupogen) for harvesting the stem cells. They also start the harvesting AFTER they've started the chemo, so there is no going back.

Obviously, they are different processes.

Deb



____________________
I just know that something good is going to happen
And I don't know when - Kate Bush
Aplastic anemia Apr/10, PRCA Jan/09, Agranulocytosis 1991
25D = 25 1,25D = 58 Aug 18/09|25D<4.8 Mar/10|10.8 Nov/12
Sep '09 q8h Nov '09 q6h
Prof Trevor Marshall
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 Posted: Tue Jun 26th, 2012 10:32

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Deb, maybe they don't need to do the chemo, but they figure it will be 'good for you'. I have spoken with pulmonologists who routinely force sarcoidosis patients to go through chemo, as it might 'kill off the disease.'
Sigh...
 
Shimon doesn't do that. Nothing except anesthetic is routinely used. I was insistent on asking this :)
 

Last edited on Tue Jun 26th, 2012 10:33 by Prof Trevor Marshall

Deb Grabetz
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 Posted: Fri Jun 29th, 2012 02:15

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Dr. Marshall,
When I went to Cleveland Clinic, in the very early stages of my diagnosis, I was only offered Methotrexate. At that point I had refused them to treat me with it because I was looking at the MP--thankfully did not go that route as I later learned Methotrexate was also a cancer drug.:?



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