Stem Cells don't work in MS brains

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Stem Cells don't work in MS brains

Postby gwa » Sat Feb 10, 2007 3:47 pm

This is some of the worst news I have seen.

gwa`


http://brain.oxfordjournals.org/cgi/con ... t/awl370v1


Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in
multiple sclerosis


Imke Metz1, Claudia F. Lucchinetti2, Harry Openshaw3, Antonio Garcia-Merino4, Hans Lassmann5, Marc S. Freedman6,
Harold L. Atkins6, Biagio Azzarelli7, Oldrich J. Kolar7 and Wolfgang Brück1,8

1Department of Neuropathology, Georg August University, Göttingen, Germany, 2Department of Neurology, Mayo Clinic,
College of Medicine, Rochester, MN, 3Department of Neurology, City of Hope National Medical Center, Duarte, CA,
USA, 4Servicio de Neurologia, Clinica Puerta de Hierro, Universidad Autonoma, Madrid, Spain, 5Center for Brain
Research, Medical University of Vienna, Austria, 6Department of Medicine, University of Ottawa, The Ottawa Hospital
Research Institute, Ottawa, ON, Canada, 7Indiana University School of Medicine, Indiana University, Indianapolis,
IN, USA and 8Institut für Multiple-Sklerose-Forschung, Bereich Humanmedizin der Universität Göttingen und Gemeinnütz
ige Hertie-Stiftung, Göttingen, Germany

Correspondence to: Prof. Wolfgang Brück, MD, Institut für Neuropathologie, Georg-August-Universität Göttingen
Robert-Koch-Str. 40, 37075 Göttingen, Germany E-mail: wbrueck@med.uni-goettingen.de



The present study analyses autopsy material from five multiple sclerosis patients who received autologous stem cell
transplantation. A total of 53 white matter lesions were investigated using routine and immunohistochemical stainings
to characterize the demyelinating activity, inflammatory infiltrates, acutely damaged axons and macrophages/microgli
al cells. We found evidence for ongoing active demyelination in all of the five patients. The inflammatory
infiltrate within the lesions showed only very few T cells and CD8+ cytotoxic T cells dominated the T cell
population. B cells and plasma cells were completely absent from the lesions. High numbers of acutely damaged
axons were found in active lesion areas. Tissue injury was associated with activated macrophages/microglial cells.
The present results indicate that ongoing demyelination and axonal degeneration exist despite pronounced
immunosuppression. Our data parallel results from some of the clinical phase I/II studies showing continued clinical
disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous
stem cell transplantation.




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Re: Stem Cells don't work in MS brains

Postby HarryZ » Sat Feb 10, 2007 9:40 pm

gwa wrote:This is some of the worst news I have seen.

gwa`


I found it interesting that very few T-cells and CD8+ cells were present in the active lesions but several macrophage cells (the garbage collectors that arrive to clean everything left over from the damage.) This is similar to the evidence that Drs. Prineas and Barrett discovered only they found no evidence of immune system activity in their work.

I'm wondering now if some of the researchers who have insisted that MS is an auto-immune disease may start to change their thinking. Perhaps this discovery will stimulate more research in other areas and hopefully find some new answers.

Harry
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Postby bromley » Sun Feb 11, 2007 6:30 am

GWA,

Calm down, calm down. I've referred this article to someone who should be able to translate it.

I don't think it means that all stem cells therapies don't work or won't work in MS brains - this is one approach. The use of stem cells (a range of different stem cells) is being researched at the moment. And as the article states:

Our data parallel results from some of the clinical phase I/II studies showing continued clinical disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous stem cell transplantation.


So this therapy was being used on patients who were very far up the EDSS scale. The general consensus among the experts is that for most sufferers, MS starts as an inflammatory disease which then becomes very much a neuro-degenerative disease. That's why anti-inflammatories (immune suppressing drugs), have little effect on SP and PP MS. And why there is a focus on neuro-protective agents / agents to promote neuro-genesis.

Dr Freedman is overseeing the Canadian Bone Marrow Transplantation study to see if this can shut down the disease in those with progressve MS. Initial results looked promising.

So the research may be saying that this treatment approach for those with very severe / end-stage MS doesn't work. That's my interpretation.

Probably best to let the dust settle. The MS which these patients had was clearly very nasty - and resulted in their deaths (which sort of makes a mockery of all the National MS Society websites which state that MS is not a fatal disease!).

So cheer up - and I might send you some more chocolates to help.



HarryZ,

It's Barnett not Barrett. I've told you before. :(


<shortened url>

I think I'll employ you at airports to uncover suspect packages. You have an amazing knack of sniffing out bad news stories related to MS (previous to this was the Rituxan PML story). Please post a good news MS story some time - it will be good for us and for you. I'm sure you're a positive sort of guy underneath. One infusion of Tysabri would do you the world of good. :)

Ian
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Postby TwistedHelix » Sun Feb 11, 2007 6:45 am

Hi gwa,

Although at first sight this does look like disappointing news, I wouldn't be too disheartened just yet. I think it was Bromley's neurologist who used to talk about a "toxic environment" in the CNS of people with MS -- in other words, something in the environs which is actively preventing neural tissue from regenerating. If we can discover what that is, I believe we'll find that the brain has a remarkable ability to repair itself.

Dom.

(edit) Hi Bromley, I hope I haven't misquoted you. Unless I missed it, I don't think the article mentioned how aggressive, rapid or advanced the MS in these five unfortunate souls was, what the cause of death was, or how the stem cells were administered... although I think you're right to assume they were pretty bad, what with being dead and all.
:wink:

no neurologist has ever told me, but I think I must be around nine on the EDSS scale, (all I have left is some use of my left arm, and speaking and eating is okay), and I've been at this point for over four years. So if my posts stop appearing............
Last edited by TwistedHelix on Sun Feb 11, 2007 7:44 am, edited 1 time in total.
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Postby robbie » Sun Feb 11, 2007 7:43 am

So cheer up - and I might send you some more chocolates to help.

Keep your chocolates !!!!!
Had ms for over 19 years now.
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Postby HarryZ » Sun Feb 11, 2007 8:05 am

It's Barnett not Barrett. I've told you before. :(


Old bad typing habits die slowly :)

I think I'll employ you at airports to uncover suspect packages. You have an amazing knack of sniffing out bad news stories related to MS (previous to this was the Rituxan PML story). Please post a good news MS story some time - it will be good for us and for you. I'm sure you're a positive sort of guy underneath. One infusion of Tysabri would do you the world of good. :)

Ian


I'm not just sure how you manage to take a reply to a posting by someone else (GWA in this instance) and say that I have "sniffed out" a "bad" news story. The story was published by MS researchers...GWA posted it...I commented on it...geez Ian, relax :wink:

Harry
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Ian

Postby gwa » Sun Feb 11, 2007 8:30 am

Harry,

I think Ian's head is already looking forward to the warm beaches of Spain with all of the scantily clad senoritas. He is just mixing up you and me temporarily.

gwa :P
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response

Postby gwa » Sun Feb 11, 2007 8:41 am

Ian,

I look forward to the response you get from the translator.

My EDSS score is getting to the point where a gymnast might be happy with the numbers. However, what is extremely happy for a gymnist translates into dead for us.

gwa
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Postby bromley » Sun Feb 11, 2007 9:43 am

Dom,

You are quite right that I was told by a leading MS neurologist that the problem was a toxic environment in the CNS. I'm assuming that this leads to the death of the myelin making cells. Finding out what causes this toxic environment will be key.

In the presentation I posted by Professor Thompson, he noted that one of the recent significant findings was the four patterns [not types] of MS.

On the downside he said that:

I suppose, we have learnt that MS is not just about these lesions that we see on the scans, but that there's also involvement of other parts of the brain that actually appear normal and perhaps also the cortex, or the outer grey area of the brain, and this is just some studies from Hans Lassman in Vienna and really showing that there's quite a diffuse change within the white matter of the brain. So it's not just lesions.


Again, this finding points to an overall toxic enviorment and away from MS being just a focal disease involving lesions. Introducing new myelin making cells looks like an interesting strategy, as long as they do not suffer the same fate.

Keep posting so that I know you haven't hit the magic 10! PM me your address (if you want) and I'll forward you a box of chocolates.


Ian


GWA, I'll be in Spain in four days time. Think of me sitting on the beach with a bottle of red wine and a beautiful woman. It could have been you if you'd played your cards right!

HZ, I only wind you up to give you something to do (I'm like a public service). I'd hate to think of you clued to the TV watching ice hockey, or whatever Canadians do.
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chocolates

Postby gwa » Sun Feb 11, 2007 10:17 am

Dom,

Ian's chocolates are very good, so send him your address and enjoy.

Ian,

I am going to Las Vegas the first week in March to celebrate my 40th wedding anniversary. Fortunately my husband didn't sit around dreaming about meeting luscious ladies elsewhere for all of those years or we would not be celebrating this date.

Hope your trip is filled with sun filled days, Lord knows that the Brits got screwed when sunshine was handed out.

gwa
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Postby Lyon » Sun Feb 11, 2007 10:25 am

bromley wrote:HZ, I'll be in Spain in four days time. Think of me sitting on the beach with a bottle of red wine and a beautiful woman. It could have been you if you'd played your cards right!
Ian,
I want to live a long life as much as the next guy but I honestly had hoped that I'd never live to see this day! I'm not even going to mention your offer to buy Dom chocolates!

On a serious note, I reached the same conclusions as you did in reading that paper regarding the five stem cell recipient autopsies. It paints a very narrow window of failure.

I wish it would/could have told more about the actual stem cell procedures which had been performed on them earlier because I imagine there have also been procedural improvements in the time since.

After the first open heart surgeries we could have decided that the percentages weren't there and it wasn't worth it but every aspect has improved since that time and people have triple bypass and return to work in a few days.

I'm sending my address and some recent pictures. I'm glad that during your recovery you found time to watch the dvd with the endless loop of the "Brokeback Mountain" love scene I sent so that it could work its magic on you.

Bob
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Postby HarryZ » Sun Feb 11, 2007 6:32 pm

Bob,

After the first open heart surgeries we could have decided that the percentages weren't there and it wasn't worth it but every aspect has improved since that time and people have triple bypass and return to work in a few days.


Many medical advancements have been made after initial failures and open heart surgery has certainly been one of them. But the big difference is that they learned from their mistakes, adjusted the procedures and eventually got it right.

The BIG problem with MS is that nobody can determine what is right or what is wrong. Take this stem cell transplantation procedure. I'm presuming they thought that by giving the patient a new immune system, the MS would be halted. But it appears that the immune system of these particular patients had nothing to do with the MS progression and thus no effect at all. IMHO, I still think that trying to play with the immune system to stop MS's progression is an exercise in futility. I believe the answer lies somewhere else and until the cause of the disease is discovered there isn't going to be any real progress in solving the MS mystery.

Harry
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Postby TwistedHelix » Mon Feb 12, 2007 6:36 am

Harry,

Many medical advancements have been made after initial failures


I agree, so perhaps this report should be filed away in the "failures" category but still, something has been discovered, even if it is when not to use stem cells, (just like many other treatments/drugs which cannot be given to everybody, but which are nonetheless effective for many).

The very first blood transfusions had a poor success rate and some catastrophic failures, all because some vital knowledge was missing, (about blood types), but the proof of principle had been established enough to encourage research into discovering why it sometimes didn't work. I think the proof of principle has been established with stem cells, so I hope a little setback won't be too much of a problem.

Just one more thought: when researchers publish their findings of a success, laboratories around the world try to replicate their work -- does the same thing happen when a "failure" is announced, or is it simply marked down as a dead end and thrown in the bin? If it is, some valuable lines of enquiry could be being discarded for want of a little extra knowledge.




I'm not even going to mention your offer to buy Dom chocolates!
Err....didn't a certain someone offered to send me his wife's Valentine's card recently? :)

Dom.
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Postby HarryZ » Mon Feb 12, 2007 6:48 am

Dom,

The very first blood transfusions had a poor success rate and some catastrophic failures, all because some vital knowledge was missing, (about blood types), but the proof of principle had been established enough to encourage research into discovering why it sometimes didn't work. I think the proof of principle has been established with stem cells, so I hope a little setback won't be too much of a problem.


I believe that somewhere down the line, stem cell transplantation is going to be a viable treatment for several diseases. But stem cell work is in its infancy and there is so much to learn about it. And there are different kinds of stem cell treatments. How many years did it take to get heart transplants done properly and that wasn't nearly as complex as dealing with diseases of the brain!

Just one more thought: when researchers publish their findings of a success, laboratories around the world try to replicate their work -- does the same thing happen when a "failure" is announced, or is it simply marked down as a dead end and thrown in the bin? If it is, some valuable lines of enquiry could be being discarded for want of a little extra knowledge.


I would imagine that "failures" are looked at closely by other researchers and they would try and determine what went wrong. If you can remember the first heart transplants all failed because of the rejection problem and how so many docs got involved to solve that issue.

Harry
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Postby TwistedHelix » Mon Feb 12, 2007 7:31 am

Harry,

You're right, of course, the brain is the most complicated thing known to humanity, (although I think mine is getting less and less complicated every day) and I think it will be a very long time before we actually understand everything about how it works. The hope I cling on to though, is that someone will stumble across something that really helps us, whether we understand exactly how or not. Understanding and fine tuning can come later. In order to do that "stumbling upon", we have to try everything which is why I think all research is important, even if it ends in apparent failure. I hope you're right about other labs picking up the research to find out what went wrong.

Ms is a bit of a chameleon in that the disease process seems to change over time so even if the later stages have nothing to do with the immune system , HSCT was still worth a shot . I am truly grateful to those peope who left their bodies to science so that our understanding can take a small step forward.

Okay, I'm off now to write my award winning screenplay -- it's a gay love story set against the beautiful backdrop of MS research...

It's called, "Setback Mountain".

Dom.
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