The World's First Successful Stem Cell Treatment of MS???

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The World's First Successful Stem Cell Treatment of MS???

Postby scorpions » Tue Nov 22, 2011 3:44 pm

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Re: The World's First Successful Stem Cell Treatment of MS??

Postby NHE » Wed Nov 23, 2011 1:28 am

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Re: The World's First Successful Stem Cell Treatment of MS??

Postby georgegoss » Sat Nov 26, 2011 12:18 am

Thanks for posting this Scorp.

From the article. . .

Researchers are continuing to develop sophisticated stem cell technology using 5g of fat as a standard, which can be expanded to 1 billion stem cells. Moreover, this technology became more efficient and convenient for patients because repetitive stem cell injections are possible from one time fat extraction. Their studies also showed the stem cell's homing effect, by which patients need less surgeries and transplants.

Although it's never mentioned in the article, it seems to be obvious this is all in reference to Mesenchymal Stem Cells (MSC).

And since they are referring to MSC colony expansion work, there is good reason to suggest from the (yet-to-be-proven clinical) science so far that this is definitely a good area to explore further.

Here's what I wrote about MSC therapy on my blog (relative to CTCI offereing the same/similar MSC therapy):

CTCI is additionally offering their own proprietary Mesenchymal Stem Cell (MSC) "infusion" therapy for MS that does not include chemotherapy (approximate cost $32K). The procedure is very similar to a phase I clinical trial currently being performed here in the US by researchers at the Cleveland Clinic. Keep in mind that this is very early study work which, by design, is not intended to determine efficacy of the treatment, but is instead intended to evaluate safety & tolerability. So the treated study-population is quite small and I would not expect to see convincing data as to how well this specific procedure works as curative therapy until a number of years from now. However, I am optimistic about this line of work and am really hoping for good clinical efficacy results because the theoretical foundation science is valid for possibly restoring some lost nerve function.

Here's the US-based MSC infusion phase I trial info. (In the title of this phase I Cleveland Clinic study they wrongly use the word "Transplantation." I really wish they had not used this nomenclature because this is not a classic transplantation procedure because it does not utilize chemotherapy and the wording is only likely to confuse some people. It is actually just a (re)infusion procedure. I'm not sure why the FDA let them incorrectly use the term "transplantation." Oh well.):

http://clinicaltrials.gov/ct2/show/NCT00813969

And here is a video report on the subject from Case Western:

http://www.youtube.com/watch?v=-S49VSZh ... r_embedded

For this therapy at CTCI, same as the Cleveland Clinic protocol, MSC's are collected from the patient's own bone marrow (probably surgically aspirated from the pelvic bone, but they may also do it by using a mobilization drug (G-CSF) and then perform PBSC collection from the peripheral bloodstream) and then the MSC's are replicated (culture expansion) ex-vivo over a period of 1-3 months to create a substantially large MSC population (in the neighborhood of 1-2 million stem cells per kilogram of body weight) and then re-infused back into the body. (Cleveland Clinic does it all via IV infusion directly into the bloodstream. Slavin does approximately 1/3 via IV infusion and 2/3 via intrathecal injections into the spinal column.)

Clinical paper (for MSC therapy use in MS and ALS):

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

The in-vitro research data with MSC's as treatment for MS looks quite promising. I'm not dismissing it, but because the treatment does not include chemotherapy to ablate self-intolerant immune cells I would not personally do it as a first-attempt treatment because I think it extremely unlikely (or impossible) that it would stop the underlying MS disease process. Although. . . . . . I might seriously think about doing it following HSCT in the possibility that it may effect repair of already-damaged nerve structure & function. However, such an effect has yet to be proved or disproved in human clinical efficacy trials. Here is the small amount of preliminary phase I EDSS clinical outcome data as presented by Dr. Dimitri Karussis which is not negative, but is also not overwhelmingly positive nor consistent and is why today (without further data) I am somewhat ambivalent about the use of MSC's for MS. (click to enlarge):

http://3.bp.blogspot.com/-fiwjmILeRFM/T ... russis.jpg

However, for everyone else considering such treatment the decision is yours, not mine. I'm just glad CTCI offers actual HSCT that includes chemotherapy that has already been repeatably-proven in population studies to be effective and enable substantial EDSS improvement following transplantation. But if you decide to chance-it and go for the MSC therapy alone without first eliminating the autoreactive immune cells of your body, don't be surprised if there is little, or no positive clinical outcome beyond a placebo effect.

Here is an article & video of a Canadian woman that received MSC infusion therapy at CTCI that appears to have worked well for her specific case. Remember that each case is likely to respond differently and her case does not directly translate to anyone else. But I have to admit, this is very encouraging and I'm glad to see the work continue:

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


The following video presentation by Dr. Dimitri Karussis who works, or worked together with Prof. Slavin describes the science behind the various treatment protocols they provide, including the MSC therapy (which I personally do not favor as first-attempt treatment but would consider it following HSCT once the antigen epitope has been rendered naive via chemo ablation):

http://www.informed-scientist.org/prese ... -sclerosis
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Re: The World's First Successful Stem Cell Treatment of MS??

Postby Liberation » Tue Nov 29, 2011 2:24 pm

Hi George,
it is a great post. Do you know if it is possible to determine before the procedure if someone's MS is caused by autoreactive immune cells? I heard from my neurologists that in circa 30% of the MS cases there is no autoimmunity involved. As far as I know autoimmunity is more likely with RRMS and not with PPMS.
Does anyone know the risks associated with the MSC treatments like in the Korean one? How safe is HSTC? I heard that there are different ways of doing chemo with HSTC.
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Re: The World's First Successful Stem Cell Treatment of MS??

Postby georgegoss » Tue Nov 29, 2011 4:47 pm

This is just my own personal position on the subject. If it sounds opinionated, it is because it's just that. My opinion. But I do think that what I'm thinking here is based on a reflection and rational interpretation of the scientifically-determined clinical and research data and I think ultimately it will be proven correct.

I think your neurologist (like most neurologists) is completely wrong. All forms of MS is caused by a dysfunction of the immune system. If it's not caused by a dysfunctional immune system, then its not MS. So this means that the underlying etiological cause of RRMS, SPMS and PPMS are all closely related and involve many (if not most, or all) of the same regulatory processes' and immune (dys)functions.

But this doesn't surprise me to hear this from a run-of-the-mill neurologist, as I have heard many times before from so many other neurologists of the same ilk. Neurologists are well-trained in nerves. But they are not educated, not trained and typically not experienced in the actual underlying (immunological) mechanisms of MS that have a hematological origin. So although the manifestation of MS results in nerve function impairment, the cause of the disease is not coming from the nerves. As such, typical neurologists do not have a clue as to how to cure MS and instead seem to fall back on the only skill left they know how to do; prescribe drugs. To date the results are not overly impressive going this drug-use route. On the other hand, ask a hematologist or immunologist about this same subject and they clearly have a good understanding as to why HSCT cures the progression of MS in the vast majority of RRMS, SPMS and PPMS patients who receive the treatment. If these were three different diseases as many neurologists assert, then the clinical data would not show such good efficacy in all three morphologies of MS. (For example, my own SPMS is 100% stopped, and my pre-existing pre-treatment symptoms have reversed / improved 40% following my own HSCT procedure). I hope that someday neurologists will either finally come around and acknowledge & support the facts of the superior efficacy of utilizing HSCT for the treatment of MS in all forms of the disease or I wish they would just get out of the way and stop being so obstructionist.

There is one neurologist that I do know of that supports HSCT for the treatment of MS. He is a rare breed. . . .

Dr. Mark Freedman, Ottowa General Hospital

http://www.youtube.com/watch?v=NhKci3UzSGE

Onto your questions. . . . .

Does anyone know the risks associated with the MSC treatments like in the Korean one?

I don’t specifically know anything about the MSC treatment in Korea, so I can’t comment on that. However, culture expanded MSC therapy is currently in phase I clinical trial at the Cleveland Clinic to determine safety & tolerability and has been done at CTCI Israel for several years now. The early work so far shows that culture-expanded MSC therapy seems to be safe with few adverse events. The main theoretical (but not yet shown to be a problem) side effect might be benign pulmonary fibroblastic growths developing if trapped in the lung tissue (MSC's differentiate into connective tissues) that would require surgery to remove. But its still too early to say if this will be a problem as so far it has not shown to be so. Time will tell, though. So far, so good.

How safe is HSTC?

The safety of HSCT has much more to do with where & how the procedure is performed, as opposed to the transplantation procedure itself. A good and experienced facility should have a reasonably low risk with a mortality rate less than 1%. But admittedly, if the procedure is performed in a slipshod manner at a low-quality treatment facility, it could be very dangerous. Something I would avoid. That’s why when I speak with people seeking HSCT for their own MS, I always encourage people to seek treatment at a reputable & experienced hospital facility that has a well-documented safety record.

I heard that there are different ways of doing chemo with HSTC.

Yes, there are two major modalities of HSCT treatment for MS in common use today. I explain about them in detail on this page. . . .

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

Sorry for my previous diatribe.

Best regards,

George
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Re: The World's First Successful Stem Cell Treatment of MS??

Postby Liberation » Tue Dec 13, 2011 1:19 pm

Hi George,
I have not been around lately, but thank you for your response. It is really valuable. I see lots of research going around lately, but I still think that stem cells have the best potential and this is the only treatment option that has a good approach.
I have also a question, I do not know what is the difference between HSTC and REvimmune therapy. My understanding was that both treatments annulate the wrongly operating immune system and rebbots it.
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Re: The World's First Successful Stem Cell Treatment of MS??

Postby georgegoss » Tue Dec 13, 2011 3:53 pm

Liberation wrote:Hi George,
I have not been around lately, but thank you for your response. It is really valuable. I see lots of research going around lately, but I still think that stem cells have the best potential and this is the only treatment option that has a good approach.
I have also a question, I do not know what is the difference between HSTC and REvimmune therapy. My understanding was that both treatments annulate the wrongly operating immune system and rebbots it.


Another great topic you bring up.

Revimmune is the brand name for the drug Cyclophosphamide (often abbreviated Cy). Cy is a very good drug that is preferentially lymphoablative that was originally developed and used for malignancies primarily associated with lymphocytes (such as Hodgkins lymphoma, etc). It turns out that it is also a good drug to eliminate autoreactive lymphocytes that are the mechanism for damage caused by hematologically-rooted autoimmune diseases such as MS.

However, it turns out that as a single-agent therapy Cy does not always work as well as desired. In the clinical trial(s) of Cy for MS (such as at Johns Hopkins), used alone the drug is unable to eliminate a large enough portion of the lymphocyte population to stop MS in all patient cases. Cy alone probably works well for those with a more benign form of MS, but doesn't always work as well for those with more aggressive forms of MS. The research continues. But so far it's pretty clear that single-agent drug therapy is not good enough to wipe out a sufficient number of autoreactive cells to cure all MS patients (but almost certainly it works better than standard immunomodulator drug therapies, such as the CRAB drugs). Complicating things is the fact that so far the researchers are unable to confidently predict which individuals will respond best to Cy therapy, even though it is clear that some people do show good benefit from Cy treatment use. . . . .

http://www.youtube.com/watch?v=SuJj52tw ... re=related

On the other hand, HSCT therapy relies on multiple drugs that are administered nearly-simultaneously that is far more effective in destroying the in-vivo autoreactive lymphocytes. Of the two HSCT protocols in use today, the myeloablative (four drug BEAM) protocol wipes out virtually all of the body's lymphocytes, pretty much guaranteeing that the "bad guys" (so to speak) are eliminated, resulting in a halting of the underlying immune attack on the body. For the non-myeloablative HSCT protocol, typically two or three drugs (subset of Alemtuzamaub, Cyclophosphamide, Fludarabine and ATG) are used to wipe out the majority (but probably not 100%, but still more than Cy alone) of lymphocytes to arrest the MS disease activity in the body. The hematopoietic stem cells that are re-infused into the body following the curative chemo regimen of HSCT is just to facilitate recovery from the chemo destruction/damage to the bone marrow, but doesn't provide any overt curative effect in themselves. Its the chemo that does that.

Lesson learned. . . multi-agent chemo (HSCT) therapy has so far demonstrated superior curative effect for a broader range of MS patients as compared to single agent (Revimmune) therapy.
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Re: The World's First Successful Stem Cell Treatment of MS??

Postby georgegoss » Wed Dec 14, 2011 3:33 pm

Just wanted to add a little more quantified data on the topic of Revimmune vs. HSCT treatment efficacy.

Although HSCT 'cure' statistics are well-understood and supported by volumous data, the Revimmune study has only so far completed the phase I trial so the treated population is very small (N=30) and has only (so far) focussed on RRMS patients meaning better treatment efficacy population statistics won't be known about Revimmune until the phase II trial scheduled to begin sometime in 2012 (so the initial results will probably be presented in 2015, at the earliest).

So here's what the comparative data (limited in the case of Revimmune) looks like. . . .

RRMS-treated patients:

Revimmune = Halting of disease activity in 66% of treated patients (out to 3 years so far and still going) combined with improvement of existing disability in the majority of the same patients.

HSCT = Halting of disease activity in 100% of treated patients (out to 8 years so far and still going) combined with 'substantial' improvement of existing disability in greater than >80% of the same patients.

Although the two procedures are not at the same development level, it's looking like the difference between the two treatments are establishing a pattern that appears clear to me.
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