Autologous mesenchymal stem cells for secondary prog. MS

[SammyJo]

This pilot study on 10 patients is from University of Cambridge, it echos the positive results from the Bristol University study on 6 patients. This study used bone-marrow-derived cells, not adipose. No immune system ablation was used. Results from 10 months after the infusion.

Title: Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.

summry: This small but significant proof-of-concept study from the UK reports initial results following the intravenous administration of mesenchymal stem cells to ten people with secondary progressive MS. A dosing regimen based on body weight was used and no serious adverse events where reported following administration, though three people experienced mild, self limiting side effects.

The authors used paraclinical assessments of the visual pathway as clinical outcome measures and as a surrogate marker of wider disease. The results seem to suggest some structural, functional and physiological improvement after treatment in some visual endpoints which might be suggestive of neuroprotection.

source: Lancet Neurol. 2012 Jan 9. [Epub ahead of print]

study weblink: http://www.ncbi.nlm.nih.gov/pubmed/22236384

[ApVish]

Glad to see more information on mesenchymal stem cell trials. It would be awesome if they stop further disability progression/attacks. But 10 months might just be too short a time frame.

Hoping for more positive news on the stem cells front.

[georgegoss]

I agree 100% with ApVish. I'm glad to see this specific work being furthered along.

I looked up more details of this specific study on the clinical trials website. . . .

http://www.clinicaltrials.gov/ct2/show/ ... 200&rank=1

I was glad to see that this study work involved colony expansion work of the MSC's to a re-infused population of around 2 million cells per kg of body weight. This appears as to now becoming a standard, same as Prof. Slavin offers at CTCI Isreal as I outline on this page:

http://themscure.blogspot.com/2011/06/g ... -have.html

Just a side note. . . this work appears to also validate the statement that the unmanipulated MSC therapy as offered by many clinics around the world (the main one being Medistem / Stem Cell Institute in Panama) as being nothing but snake oil stealing people's money for an ineffective treatment.

[SammyJo]

Thanks for your feedback George! You have been such a pioneer with HSCT - congratulations on your 2 year anniversary!

I've had CCSVI 4x over the past 2 years, the progression has stopped and I can do minimal exercise to recoup nerve function but it is slow, hense my interest in MCS from adipose tissue. I don't think I could handle anything more aggressive at this point. Most of the MS-MCS stories I've followed tend to show improvement at first, which fades after a year or so. I am hoping that restoring better circulation as the first step, will extend the benefits from MSC. I'm also searching for others who have done CCSVI followed by MSC.

[georgegoss]

Thanks for your feedback George! You have been such a pioneer with HSCT - congratulations on your 2 year anniversary!

I've had CCSVI 4x over the past 2 years, the progression has stopped and I can do minimal exercise to recoup nerve function but it is slow, hense my interest in MCS from adipose tissue. I don't think I could handle anything more aggressive at this point. Most of the MS-MCS stories I've followed tend to show improvement at first, which fades after a year or so. I am hoping that restoring better circulation as the first step, will extend the benefits from MSC. I'm also searching for others who have done CCSVI followed by MSC.

Also, it seems we are at the start of MCS treatment in the US, obviating the need to go to foreign clinics. I will start a new post on what I've been able to track down on Celltex in Texas.

Thanks Sammy.

As it stands now, no US facility can legally provide/administer colony-expanded MSC therapy outside of an FDA-approved clinical trial (as currently only performed by Cleveland Clinic / Case Western). The data is so far stacking up that only the colony-expanded MSC therapy (and not the minimially manipulated adipose fat tissue MSC therapy) appears to have a potentially beneficial effect. So at this point in time the only option of legally receiving such treatment outside of a trial is an overseas clinic, such as CTCI in israel. The rules may change someday in the US, but for now it's pretty black and white. Effective MSC treatment cannot be had in the US outside of a clinical trial at this time. But as stated before. . . . I'm glad it is available somewhere, such as in Israel with Prof. Slavin:

http://www.ctv.ca/CTVNews/Health/200811 ... nt_081116/

And the US-based trial work at Case Western:

[SammyJo]

I hope there will be more news soon for IRB approved trials for MSC stem cells.

[georgegoss]

Thanks for educating me about this, Sammy. Clearly there is more to the story than I had first understood.

Although MSC culture expansion in the USA is clearly illegal by FDA rules & regulations, it looks like Perry's efforts to support and push a bill/law through the Texas state legislature and support a business endeavor clearly makes it legal under Texas state law. I don't know how this will eventually be reconciled between federal and state law, but in the end I hope Celltex will be able to provide this (culture expanded) MSC infusion therapy without breaking any laws and available to the public as a whole. (This situation appears to be similar to marijuana being illegal under US Federal law, but legal under specific circumstances for medical use under some states law, such as California.) I fully support this expanded MSC infusion treatment endeavor since 200M MSC's as you described over three infusions fulfills the basic researched efficicacy requirement of greater than 1-2M stem cells per Kg of body weight. I suspect in the end we'll see if this is challenged in Federal court by the FDA. But for now I'm glad to see the work continue. I personally would also consider this treatment for myself if the stated MSC expansion population is correct. And if so, the $25K pricetag might be a good value making the treatment well worth a try.

Good news summary of the legal/political situation (be sure to watch the video):

http://www.msnbc.msn.com/id/44291973/ns ... tors-firm/

[Liberation]

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[georgegoss]

Anyone knows where someone can participate in a clinical trial with MSC stem cells in Europe? In last august there was an announceent that clinical trails will start in 6 months all over in Europe for 150 patients.

Anyone knows what are the differences in efficiency and safety among the different MSC stem cell sources (like, fat, bone marrow, umbilical cord blood, etc.)?

I am a little bit confused what is the mechanism of MSC stem cells therapy. Are they supposed to repair the damage caused by MS or they are only neuroprotective?

All excellent questions, Lib. At this point the data is so sparse that all the questions regarding the underlying mechanisms of possible benefit are still unanswered. There have been a few basic phase I (safety & tolerability) studies, but they were very small patient populations and were designed to test safety, not efficacy. The next levels of phase II / III studies are designed to test efficacy, but have yet to start.

As of today, this study report out of Israel is the best compilation of scientific clinical data (which frankly, is not very conclusive):

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036569/

Here is an article describing the European study out of the UK you mention that will be treating 150 patients. But again, this early study is designed to primarily test safety, not efficacy. If you want to participate in this study, I would suggest to contact the Imperial College London:

Doctors begin major stem cell trial for MS patients

http://www.bbc.co.uk/news/health-14332206

Cleveland Clinic is also doing a phase I study:

http://www.healthcanal.com/drugs-approv ... y-for.html

And some Case Western researchers in a video report about this subject:



Here is an article & video of a Canadian woman that received MSC infusion therapy at CTCI Israel that appears to have worked well for her specific case. But remember that this one case doesn't prove anything specific and does not directly translate to anyone else:

http://www.ctv.ca/CTVNews/Health/200811 ... nt_081116/

If you can't / don't get into the UK study, you can still pay to get the MSC treatment at CTCI in Israel:

CTCI homepage:

http://ctcicenter.com/

"In-vitro" (in the test tube) cellular observations have shown that MSC's secrete cytokines that are thought to operate as messenger molucules to encourage or direct other cells to effect repair of nerve tissue. There is also some preliminary evidence that MSC's (in sufficient population quantities) "might" have some immunomodulatory effect (duration unknown) to reduce autoreactivity underlying MS. However, there is virtually no "in-vivo" (in the body) data to show clinical benefit in a controlled or repeated manner. So right now scientists are "hoping" that what has been observed at the cellular level will translate to benefit in a higher level functional organism (human body). So this is why population studies and trials must be performed. Until then, all these very important questions remain unanswered and there is only individual anecdotal information, which in itself does not hold any predictive usefulness as a treatment for MS.

The only "real" conclusions that have been determined so far is that 1) The re-infused MSC's must be culture-expanded to create a sufficiently large population (1-2M MSC cells per kg of body weight) to create some clinical effect (which also clearly shows that clinics, i.e. Panama, that do not manipulate the MSC population is completely ineffective and is snake oil rip-ff), and 2) The re-infused autologous MSC's so far appear to be safe. But beyond this, there is no conclusive evidence that this treatment is responsible for improving people's health. Although, the data is definitely encouraging and seems to point in the right direction.

This is why I'm happy to see the work continue in a controlled manner. If the results progress along as everyone hopes, I also would consider this treatment.

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[georgegoss]

Whether the efficacy could be improved by repeating the stem cell therapy? Could a much more impressive gain be achieved this way?

This has not been studied. But it seems to me that if a single MSC infusion turns out to be clinically beneficial then it is logical to think that multiple MSC infusions may offer additional benefit. However, this approach may also require some additional safety testing because there is a 'theoretical' possibility that infused MSC cells may lodge in the pulmonary tissues causing benign fibroblastic growths that could impair breathing function. If so, then lung surgery may be required to remove them. But this is still only a theoretical possibility since it has not yet shown to be a problem.

What differences can the different MSC sources (bone marrow, fat, etc.) result in efficacy and safty?

This is truly an excellent question. Mesenchymal Stem Cells reside in several descrete locations within the body (bone marrow, adipose tissue, cartilage and other connective tissues), and I also wonder what is the difference, function and capability of these MSC's in relation to each other. At the molecular level, these various-origin MSC's appear to be slightly or somewhat morphologically different, even though quite similar in function. Do all MSC origin-types behave the same, or differently in terms of clinical benefit for neurologic functioning? (It is known that marrow-derived MSC's replicate more effectively as compared to adipose MSC's, so clearly there is something different about them at some level.) In other words, is an MSC an MSC an MSC? I spoke with a PhD researcher at the Cleveland Clinic where they are doing the phase I trial with MSC's for MS (they use them from bone marrow because they can replicate them for colony expansion purposes more easily) and asked them this same question. The response is that they don't know. No one (yet) seems to know which source MSC might be better than the others, or if certain types have superior clinical performance, if at all. All part of the remaining mystery yet to be solved.

The story of the lady who plays golf was very impressive.

I was also very impressed with her recovery. Good to see. But was it due to the use of MSC infusion therapy, or just a propitious coincidence? No one knows the answer because a single individual's isolated case tells us almost nothing. This is why I am very happy to see these larger treatment population trials being conducted as only a controlled population study will provide the answers.

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[packo]

http://www.chron.com/news/houston-texas ... 688266.php

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