This Is MS Multiple Sclerosis Community: Knowledge & Support

Hi elliberato

My procedure was very similar as what Dr. Burt is performing at NWU. However, it's not identical. Dr. Burt's procedure is "lymphoablative" and my procedure was "myeloablative." Basically my protocol followed the HALT-MS clinical trial protocol as established by Dr. Richard Nash at the Fred Hutchinson Cancer Research Center in Seattle. So far both protocols have consistently shown substantially similar curative efficacy.

Hi George
Congrats for your improvements This treatment sounds very interesting.
Does the Univ hospital in Heidelberg offer it to MS patients on a general private basis or were you included in a clinical trial? (sorry if your blog might reveal that and I did not see it yet).

Thanks, Steffi

Hi Steffi,

Thanks for your bestwishes.

You have zoomed in on a very nice question. The reason I went to Heidelberg is because I could not qualify for any of the clinical trials in North America (because I was SPMS) and was able to receive treatment in Heidelberg as a private patient, no strings attached. I'm sure Heidelberg would be likely to treat any suitable patient with clinically-definite MS that is not PPMS.

As a privately treated individual I did find several positive aspects to the treatment in Heidelberg as opposed to participating in a clinical trial:

- Did not have to meet exceedingly difficult (and often rediculous) inclusion/exclusion criteria. The Heidelberg criteria is based on wether or not the treatment is likely to be beneficial for a specific individual. Clinical trial criteria has nothing to do with curing a specific individual. The purpose of a trial to prove/disprove hypotheses' in the context of a population. These are two totally different objectives.

- Not required to participate in onerous follow-up study activities. (When the treatment was complete I was done and could get on with my life without further travel & distraction of more required study work).

- The procedure in Heidelberg is substantially less expensive than US-based clinical trial treatment (less than half the cost).

- My underlying MS disease activity is 100% stopped and my MS symptoms are substantially improved. Clear evidence that the treatment can work well for SPMS cases.

For anyone that is not familiar with the curative aspects of the treatment for MS. . . .

http://themscure.blogspot.com/2010/06/s ... rence.html

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They stated that they do not treat PPMS cases ?

Honestly I'm not 100% certain. I did not specifically hear that they absolutely would not treat PP cases. However, I have seen their new questionare they send out to patients to complete as part of the process to apply for treatment. Based on these question they "seem" to correctly understand (based on current research and clinical trial data) that earlier stage RR stage cases fair better with the curative aspects of HSCT as opposed to later stage PP cases. (I was in the middle of the spectrum with SP, but also fully ambulatory and it worked very well for me.)

I have been in contact with a guy that has early-stage PP (he is still ambulatory) and he would like to get HSCT at Heidelberg. His goal is just to "stop" his disease process before he becomes disabled in a wheelchair. Based upon the clinical data I think that can be accomplished with HSCT. (Most PP cases will see a halting of their disease activity. If I were in his same situation I would go for HSCT treatment.) So I am going to arm him with the relevant clinical data and argument concept so that he can apply for HSCT since I think he is likely to see benefit. Once he goes through the application process I will let you know what happens. However, even if he is rejected the procedure can still be had at the Apollo hospital network in India (they will treat anyone with any disability status). I personally just favor Heidelberg over anywhere else due to their treatment safety record.

Just my personal opinion consistent with the clinical trial data. . . if someone is PP with EDSS >6.0, there is probably not any significant benefit to the treatment and I probably would not do it if in the same situation. (But EDSS <6.0 is a different story.)

Just for reference. . . . the phase I clinical trials focussed on the most severe (EDSS >6.0) progressive cases of MS. This is where they first discovered (almost by accident) that RR cases repond better to treatment. You can check out this technical paper summarizing the results. Specifically look under the section "RESULTS OF FIRST-GENERATION HSCT PROTOCOLS FOR MS."

http://pegasus.fmrp.usp.br/projeto/arti ... igo113.pdf

And overall list of many technical references that I have compiled if anyone is interested to know more. . .

http://themscure.blogspot.com/2010/06/s ... rence.html

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George,
My neuro feels i am entering into the spms stage. I have been in contact with Heidelberg and just sent all my info. Unfortunately I am already >6.5 and only in four short years. After reading your reports and supporting info it seems that I would not fair too well with the treatment? I am only 42 and kind of in panic mode now as I can only walk a step or two without having to sit down...I have had stable MRI for three years and no enhancing lesions. It appears I may just be fucked period?

I'm sorry to hear about your detrioration status. But don't panic yet. Like everything in nature, with MS there are no certainties. Just "probabilities."

My understanding is that based upon the limited clinical work done so far on progressive cases is that there may be some underlying clinical differentiation between SPMS and PPMS activity. (Although the specific etiological difference has not yet been explained by anyone.) My own personal thinking is that HSCT should be used for all RRMS and SPMS cases (regardless of EDSS score) and that HSCT use should be restricted to those that are PPMS with an ambulatory disability status (EDSS <6.0). As I am not a doctor this is just my own personal opinion from all the medical & technical papers that I have read.

Definitely HSCT has overwhelmingly positive efficacy in RRMS and also SPMS<6.0 populations. But there are individual demonstrated cases of advanced progressive cases that have seen clinical improvement with people greater than >6.0. And even so, it is more likeley-than-not that the disease progression will be stopped in such advanced cases, regardless of disease status.

Specifically because you are SPMS (and not PPMS). . . if I happen to be in your same shoes, for myself I would try to get HSCT as soon as practically possible (since the deterioration seems to accelerate, on average, when the disease gets to higher EDSS score levels). Most likely, if you can see some reversal of symptomatic deficit (which is entirely possible) then it probably would manifest as slow improvement over a longer period of time (similar to the way stroke patients can slowly regain functioning over time). Just my two-cents worth.

If convenient for you I would appreciate knowing the response from Heidelberg (if they accept you, or not). Only if you want to share the info, of course. I will keep my fingers crossed for the answer to come back yes. At least at that point then you can decide for yourself.

Just to share some info from a technical paper on this same (primary progressive) subject from the early phase I HSCT clinical trials that focused on late-stage progressive MS. After the researchers compared treatment efficacy between progressive and relapsing forms of the disease, they quickly discovered that HSCT is "less effective" (but not completely ineffective) for PPMS cases as opposed to RRMS and SPMS cases. I refer you specifically to this paper titled "Hematopoietic Stem Cell Transplantation for Multiple Sclerosis" from 2005:

http://pegasus.fmrp.usp.br/projeto/arti ... igo113.pdf

And specifically this passage. . . .

In a European retrospective analysis of 85 patients,
the progression-free survival at 3 years was 78%
in secondary progressive MS and 66% in primary progressive
MS At Northwestern University, Chicago, Ill,
of 21 patients with secondary progressive MS treated using
a myeloablative HSCT regimen, disease progression
in more disabled patients with a pretreatment EDSS score
of 6.0 or higher was significantly worse compared with
those with an EDSS score below 6.0. In fact, none of
the 9 patients with an EDSS score below 6.0 had disease
progression worsening by 1.0 or more EDSS points after
more than 2 years of follow-up.

I find it interesting that there is a clinically-differentiated curative efficacy population result between PP and SP at equivalent EDSS levels. I have found no theories offered to explain this phenomenon. Clearly PP and SP disease activity are both dominated by axonal dystrophy. I can't imagine how the two cases would differ.

Bottom line. . . Clearly progressive (PP and SP) patients see less overall curative benefit from HSCT (but that does not mean “no” benefit.). Overall advanced PPMS cases (EDSS >6.0) still "stopped” or “halted” the underlying progression of the MS disease process in approximately two-thirds of this PP progressive population, and nearly 80% of the SPMS population. And although not clearly demonstrated (the clinical trial population was too small to draw such a final conclusion), there is indication from the SP population that being PPMS with an ambulatory EDSS bodes particularly well for achieving curative results as opposed to cases that are not ambulatory.

A couple other items to note regarding this paper. . . .

- TBI is no longer used in any HSCT protocol for treatment of MS because it has been found to be unhelpful under all circumstances. In fact, it is the most detrimental part of the initial study protocols, responsible for the deaths that had occurred at that early study stage. TBI is no longer used and there have been zero deaths in the phase II chemical-only protocols.
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- The BEAM protocol is the gentlest & safest of the myeloablatiove chemo protocols while simultaneously being efficacious. A good regimen for this treatment.

Based on this info if I were PPMS, regardless of disability status, I personally might attempt to get HSCT to stop my own disease. There is a chance that my disease would be stopped, and a lesser chance that it would not. For me, better-than-even odds is superior to thinking there is nothing that will work. And being SPMS, that would likely fair even better.

I think there is an argument to be made that this treatment has a reasonable chance of achieving the objective of “stopping” or “halting” of the underlying MS disease activity & progression for PPMS and advanced SPMS cases. If that is achieved, it could at least bring a better degree of certaintly to the future of one’s life. And there’s also the possibility that some symptomatic improvement following HSCT could be seen. Only time would tell for any given individual in that area.

http://themscure.blogspot.com/2010/06/s ... rence.html

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Thanks George for all your work and help here.

i am happy to hear about your improvements, George.
As for the effect of this treatment for PPMS and even RRMS, we have to consider the fact thet we still do not know what is causing MS at the ifrst place. There has been an increasing number of research (most of which has involved the postmortem examination of the CNS lesions of deceased MS patients, the "youngest" of these lesions showing no signs of immune cell involvement) that appears to demonstrate that the immune response seen in MS is secondary to some other process that attacks the CNS, to which the immune system then responds. In other words, "autoimmunity" is looking more and more to be a symptom than a cause of MS, and this calls into question the long-term efficacy of approaches that "reboot" a patient's immune system, since the underlying cause of the disease remains unaddressed. My personal feeling is that what we consider MS is only a bunch of symptoms and the cause of these symptoms vary person by person.

It is still not understood "why" MS occurs. But it is well understood "what" is happening in individuals with MS.

As for cause. . . The general prevailing (unconfirmed) belief among scientific professionals is that a genetically susceptible individual is exposed to a yet-to-be-identified environmental antagonist in a vulnerable individual that initiates the neurologically-damaging immune self-intolerance of MS. I have heard the apt analogy that genetics loads the gun and the environment pulls the trigger. Clearly more elucidation is required in this area.

However, the "scientifically-valid" data indicating the mechanistic action of MS is stacked so overwhelmingly in favor of an autoimmunity pathology that no other theory even comes close. Nowhere near.

According to these researchers at Wayne State University, the autoimmunity model is not a therory. They consider it fact.

http://www.physorg.com/news/2011-02-pub ... ebate.html

Researchers publish results settling multiple sclerosis debate
"This work is significant because for the first time we are able to definitively establish a cause-and-effect relationship linking the marked T cells to the development of relapses and show unambiguously that it was the same T cells that mediated relapsing cycles."

As for stem cell transplantation (HSCT) to reboot the immune system and cure MS, it would be quite hard to beat the already-established 100% success rate for RRMS patients that have had their underlying disease activity stopped as shown in several clinical trials to date.

Scientists Reverse Early MS With Patients' Own Stem Cells

http://www.medicalnewstoday.com/articles/137238.php

After an average follow-up of three years after receiving their transplants (which took place between January 2003 and February 2005), 17 patients (81 per cent) improved by at least one point on a [EDSS] disability scale. And for all [100%] patients, the disease had stopped progressing.
.

It turns out that Heidelberg will likely treat PPMS cases (based upon alignment with the patient "expectation" of treatment, which is a little less efficacious as compared to RRMS and SPMS cases, but likely will still stop the disease progression).

In fact, I have been communicating with a PPMS patient that will be going to Heidelberg next month (May, 2011) that is planning to receive the same HSCT BEAM treatment I received. I'll let you know what happens.

Curious to know about this PPMS patient in Heidelberg and what happend with him during last year? And what is the usual "waiting time" after application, taking into account that money arent the problem?

Hi czapski-

I was initially approved after sending medical records and application to Heidelberg. After traveling all the way there though and meeting with their neurologist, I was denied treatment primarily because I could not show history of immunomodulator drug history for effect on my m.s. This is taking into account the fact that PPMS has no FDA approved drugs to treat. I am aware of a few others who were initially accepted at Heidelberg only to be denied treatment for "marginal" reasons. They have some definite cracks in their acceptance criteria and process especially in communication between departments in my opinion.

Long story short I was back home in a week totally disappointed that my journey was turned into a tourist trip. I then pursued HSCT at CTCI in Tel Aviv and had the treatment and transplant completed 8-24-11.
I am now 7 months post transplant and hoping for good things from the treatment. We will see, it will take another year to determine success.

HUD

The alternative here is that there are two facilities that will treat PPMS patients as follows:

Myeloablative (BEAM) HSCT protocol = Manipal Hospital in Bangalore India. Their first PPMS patient was treated there 7 months ago and I spoke with her husband (Richard) yesterday and he told me that her disease is stopped and she is already reporting some modest symptomatic improvements (reversal) in some of her existing MS symptoms. I think the 12-24 month post-treatment timeframe will be most telling for how things unfold for her. But since their main objective was simply to halt the progression of the disease, they have already expressed satisfaction with the tretment. Any improvements from here on out is an added bonus. Since her hyper-sensitivity to heat has already resolved, this bodes well for further symptomatic improvement to come.

Non-myeloablative HSCT protocol = CTCI in Tel Aviv, Isreal where HUD went to have treatment for his own PPMS as he describes.

The contact info for both facilities are listed on this page:

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