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Stem cells for MS

Posted: Fri Nov 14, 2008 3:40 pm
by mrhodes40
Here is the abstract from pubmed on the Karussis stem cell work (NOTE there is no chemo in this treatment it is JUST stem cells):
Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases.Karussis D, Kassis I, Kurkalli BG, Slavin S.
Department of Neurology and Laboratory of Neuroimmunology and the Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Karem, Jerusalem, IL-91120, Israel. karus@cc.huji.ac.il

Bone marrow (BM) derived mesenchymal stem cells (MSCs) (non-hematopoietic, stromal cells) can differentiate under certain circumstances into cells from various neuronal and glial type lineages; they also exert immunomodulatory effects. For potential clinical applications, BM-MSCs offer significant practical advantages over other types of stem cells, since they can be obtained from the adult BM (the patient himself being the donor) and can be easily cultured and expanded posing in parallel a very low risk for development of malignancies. We have shown that BM-MSCs cultured with a cocktail of growth factors (containing FGF and BDNF) differentiate into neuronal/glial lineage cells with a predominance of cells expressing astrocytes' markers. BM-MSCs were effective in suppression of chronic EAE in mice and induced neuroprotection, preserving most of the axons in the CNS of successfully-treated animals. Histopathological studies revealed that MSCs could efficiently migrate into the CNS inflamed tissue (both when administered intravenously and intraventricularly) and differentiated into cells expressing neural-glial lineage markers. Our preclinical results indicate that bone marrow can provide a source of stem cells with a potential for migration into inflamed CNS tissue and differentiation into cells expressing neuronal and glial cell markers. Such an approach may provide a feasible and practical way for in situ immunomodulation, neuroprotection and possibly remyelination/regeneration in diseases like multiple sclerosis. We therefore developed a explorative protocol for the evaluation of this therapeutic approach in a small group of patients with MS and other neurodegenerative diseases.

PMID: 17610906 [PubMed - indexed for MEDLINE
Note that one of the things most often leveled as a probable problem with this kind of approach is that it wouldn't get to the brain and that even if it did it might not become useful cells. This seems to indicate that is not the case. It also indicates that immunomodulation is possible this way, an apparent fact also borne out by studies in RA with this type of stem cell approach.

In fact it is true that it has been years since mice with strokes were given stem cells peripherally that clearly regenerated tissue in the brain(the stem cells were marked with a special dye); stem cells know where inflammation is and "go there" on their own to heal.

I couple this interesting work with the comment from the article below, which was on people with progressed MS who had the other kind of stem cells transplant with chemo
from here
http://members.cox.net/marty.altman/Pag ... Marrow.htm
"We weren't looking for improvement," Freedman told a stem cell seminar at the U.S. National Institutes of Health. "The actual study was to reboot the immune system." Once MS is diagnosed, Freedman said, "you've already missed the boat. We figured we would reboot the immune system and watch the disease evolve. It failed." They had thought that destroying the bone marrow would improve symptoms within a year. After all, MS is believed to be an autoimmune disease, in which immune system cells mistakenly attack the fatty myelin sheath that protects nerve strands. Patients lose the ability to move as the thin strands that connect one nerve cell to another wither. Instead, improvements began two years after treatment
My assumption about these newer types of stem cell therapies is that they too may result in "late"improvements perhaps a log time after the therapy. It's too soon to know yet! But to be quite honest, chemo is so very hard on the body ( there is some brain atrophy just from that phase) that I am very curious to see if there are better late improvements in this group that got the stems with no ablation.

I also believe personally that it is likely these therapies will need to be repeated periodically, but I read another paper by the reseach team that said they would apply for a further study grant and it estimated the cost to treat each person would be 20 thousand dollars.

Well, 20k is a lot but it is what I believe copaxone costs per year and is about half tysabri and rituxan costs. This type of therapy should be not only potentially better than others but it also may be more economical.

There are of course places supposedly offering this type of therapy now in CHina and Central AMerica. I wish some people who did it would start a regimen page........
:D

Re: Stem cells for MS

Posted: Fri Nov 14, 2008 6:04 pm
by CureOrBust
mrhodes40 wrote:There are of course places supposedly offering this type of therapy now in China and Central AMerica. I wish some people who did it would start a regimen page........
Something like this maybe? http://www.freewebs.com/margoliver/margosblog.htm
Which was pasted back in feb on the thread http://www.thisisms.com/ftopicp-35620.html#35620
Although she way far from 2 years in now.

Posted: Sat Nov 15, 2008 8:26 am
by mrhodes40
Hi Cur-o
yes that is the kind of thing I mean. Her results sound pretty equivocal, though she is considering a second trip if she can raise the money,so she felt somevalue was there. Perhaps she'll see more changes as time goes on!

There is a forum for people who've been to china that is pretty upbeat about the treatment with the fervor of true converts on the other hand I have written to a young man who had treatment in China then came home and 9 months later had an MRI with 9 new lesions--it did not help him at all and he went on tysabri.

But the devil is in the details: I believe that kid had cord blood, not mesenchymal stem cells, and I am not sure where it was placed: intrathecally (the CSF) or peripherally. Such things would be important to know. He was also progresssed and had severe and raidly evolving MS at a young age , which is kind of a different animal.

The people on the china forum with MS seemed to be mainly folks with recent diagnosis. That makes a huge difference.

My personal MS journey was terror at diagnosis and compulsive neurotic preoccupation with what was going to happen, constantly concerned about how I felt and every little thing I felt that seemed different somehow caused me to obsessively evaluate what I had eaten and done in the last day trying to get contol of the MS; I was convinced it was a disease a person COULD control if only I could understand the vitamins and foods required to do so.

Eventually I realized that I really had slow moving MS. I could still jog at 6 years. By the time I had had MS for 4-5 years I knew what my "pattern" was, but before that, I was just scared to the point of terror all the time. I'd say PTSD could have been the diagnosis for that mental construct!

Every time I meet someone who had MS for a year or two then did some kind of treatment that they now claim cured them I take it with a serious grain of salt because they may well have no clue what their MS pattern is. If they are like I was, then they can certainly compare their "mild" pattern to the imagined, feared future and find themselves greatly heped by the treatment they chose, whether that is true or not.

If I had gone to China in year one I undoubtedly would have attributed my mild pattern to that treatment. OTOH, maybe it would really kick MS's butt if you do do it early on like that! I hope we learn more quickly, hopefully people who've undertaken the "out of pocket" trips will share more of their stories and a pattern will emerge about which type of treatment helps and how often it needs to be done and for how long it lasts.

That comment by Freedman that they had unexpected improvements at 2 years really plays on my mind; he attributes those improvements to neuro regeneration that just took that long to be apparent.

If that is true for everyone then it may appear that treatment was less successful than it really was in the near term. That could make it hard to evaluate.
m

Posted: Thu Nov 20, 2008 5:48 pm
by cheerleader
Not sure if you saw this, Marie...
more on mesenchymal stem cells. A golfer with PPMS goes to Israel...
Canadian Louise Zylstra is a golf pro who was diagnosed with rapidly progressive MS in 2007.

By early this year she was not only unable to play an 18-hole golf game, but she could barely walk 50 yards.

"Her course is primary progressive and right now we have no sure treatments for primary progressive disease," neurologist Dr. Mark Freedman, an MS specialist at Ottawa Hospital, told CTV News.

Primary progressive MS accounts for between 10 and 15 per cent of cases and does not often follow a predictable disease pattern, Freedman said.

Freedman told Zylstra that within two years she would likely end up in a wheelchair.

"It was a disaster," Zylstra told CTV News. "When you think, I might not play golf again and that's what you do, it's like, what am I going to do?"

Eight months after travelling to Israel for the treatment, Louise is back on the golf course.

"It's night and day," Zylstra said. "It's a complete 180 from where I was."

Given the progressive nature of Zylstra's MS, such a recovery would have been highly unlikely without the treatment, Freedman said.

"She's recovered substantial function very quickly," Freedman said. "She's out golfing, and out-golfing most people, which is quite incredible."
link

Posted: Fri Nov 21, 2008 11:30 am
by mrhodes40
Good Lord CHeer! You found an article with both doctors in it!!! Freedman from Ottawa and also the Israel center that Dr Karousssis is in!

That is awsomely cool. Man, I sincerely wish it was being tested here somewhere. I'd fly anywhere to try it in research, but I am not in a situation where it is reasonable to go to central america and do the for profit clinic they have there, we can't afford it for an experimental treatment, but the more we see of these articles the more likely it will be that it will be available here. I might hold a giant bake sale if the results keep looking so positive.

It comes down to this: if it is a cure (meaning it makes a significant dent in the ability to get around even if not back to normal) we'd gladly spend any amount of money to improve quality of life, but if it's just a roll of the dice then 40,000 could buy me a very nice wheelchair if I need it and fund my dearly beloved husband's retirement. I'm not keen on making other people rich for when they cant offer any assurance.

But I do know other people have done it and really wish they had a regimen page and would document the results over the following year or two. Thanks for the good story of that lady with the progressive MS...
I love it that Freedman was the person who commented on the study participant.

I just wonder what he is thinking about it, he is, after all, the guy who noted the two year improvements after the stem cell transplants with the dangerous chemo componenet. I wish I knew what he is thinking about it all now! This gives me hope maybe it won;t be too too long...

marie

Posted: Sat Nov 22, 2008 1:07 pm
by mrhodes40
Here is a link to a commercial site for the x-cell center in Germany. THey have a tally of results on this page for MS patients treated.

http://www.xcell-center.com/treatments/ ... rosis.aspx

The results are again kind of equivocal with 11 of 19 showing noticeable improvement and 7 the same with one deteriorating. Really short follow up on that call back though, I mean seriously, 6 months? ONE month for some of them? Puhleeze...... I wonder if more will happen given more time, back to Dr Freedman's comment that they had an unexpected and surprising improvement at the 2 year mark.

And again the devil is in the details, these were hematopoietic stem cells not specifically mesenchymal stem cells which appear to be in some studies the ones specifically needed for MS.

Overall though fairly positive.

Posted: Sat Nov 22, 2008 1:15 pm
by mrhodes40
THis paper is included in whole and is about mesenchymal cells specifically and their ability to differentiate into neurons, WORKING neurons in this case rather than the nonfunctionqal ones reported before

http://stemcells.alphamedpress.org/cgi/ ... l/23/3/383

cheerleader

Posted: Mon Nov 24, 2008 8:33 pm
by Cojack
HI,

did the article describe what they did to the golfer? also, wasn't there just a mesh stem cell failure in human spinal cord recently?

jack

Posted: Tue Nov 25, 2008 10:56 am
by mrhodes40
Hi cojack,
Yes, this link, as cheer also added it above, tells that it was mesenchymal stem cells at the same center listed in the first paragraph of this thread in Tel Aviv.

<shortened url>

A mesh in a spinal cord is different. Could be the mesh that failed, the type of cells, the size or location of the lesion, who knows? It does not have as much to do with this treatment we are talking about as it might seem when you see the words "stem cells".
marie

Posted: Tue Nov 25, 2008 11:06 am
by cheerleader
mrhodes40 wrote:Good Lord CHeer! You found an article with both doctors in it!!! Freedman from Ottawa and also the Israel center that Dr Karousssis is in!

That is awsomely cool. Man, I sincerely wish it was being tested here
I just wonder what he is thinking about it, he is, after all, the guy who noted the two year improvements after the stem cell transplants with the dangerous chemo componenet. I wish I knew what he is thinking about it all now! This gives me hope maybe it won;t be too too long...

marie
You and Mark have kept my eyes on this prize...I believe what they are doing in Tel Aviv is the way. Healing the endothelial component of the blood brain barrier is it, and adult stem cells do just that. You can kill every bugger, virus and bacteria with chemo, and slow down MS, but that will not seal up the endothelium...(it actually damages it and makes it more permeable in the long run, which is why cancer and heart docs of the European Science Foundation just met in Europe to discuss the endothelium)

http://www.sciencedaily.com/releases/20 ... 081057.htm

I say, start making brownies for the bake sale. This is a much better way to spend your 40 grand, Marie! I predict the next three years.
Happy turkey day to you!
cheer

Posted: Tue Nov 25, 2008 12:26 pm
by mrhodes40
Hey Cheer
it actually damages it and makes it more permeable in the long run,)
Yes many things we do cause other problems in the MS world; I had read that the chemo part of HSCT actually causes brain atrophy!

but stem cells of your own creation with no chemo, which is literally nothing more than you giving yourself a specialized blood transfusion, is safe. NO immune suppression, as long as there is not ablation there is not any risk of damaging the brain with the chemo part of treatment as was done in the first "stem cell transplants" and no other side effects from chemo drugs like hart damage or kidney damage etc.

What I find FASCINATING is that these stem cells are modulating the immune system themselves without the chemo involved at all. If this turns out to be consistently true and durable what a boon! And it makes you wonder how much of the stem cell transplants with chemo in the past which showed some positive effects were actually all caused by the stem cells, NOT the chemo part of it at all!

I am waiting with bated breath for more along these lines........even if you think MS is probably infective as I believe, healing the BBB and potentially regenerating some nerves down the road this way is still a great treatment. Who knows, could it be stems heal infected inflamed cells? If it works I'd be glad to let the researchers figure out why later...
i just want it...soon!
Wanna buy some home made toffee?
8)

Posted: Wed Nov 26, 2008 5:24 am
by CureOrBust
mrhodes40 wrote:What I find FASCINATING is that these stem cells are modulating the immune system themselves without the chemo involved at all.
I personally question if its the stem cells or something else in the "soup" they would inject as part of the treatment?

Posted: Wed Nov 26, 2008 9:33 am
by mrhodes40
Hi Cur-o
Well, they are saying it is the stem cells, if you read the first abstract in this thread the author mentions the fact that they *are* immunomoduatory.

There are a number of papers on that aspect of stem cells, not just one chance mention.

The stem cells are multiplied in the lab in order to get the numbers required for this, and that is done with growth factors like insulin like growth factor. Otherwise the stem cell transplant is just like a blood transfusion, it comes in a red bag that is obviously blood that the patient gets intravenously, and that's it. No other drugs are in there.

I do not know if the small amounts of growth factor that might possibly be left over would modulate the immune system and the stem cells be somehow a useless red herring, but it seems unlikely in my mind. You can't give drugs in a transfusion line or anything because blood products have to be unadulterated and pristine or they break down and become worse than useless. With this background, I do not understand the "soup" reference, blood products are always really pure and plain. :?
marie