Why?

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Why?

Postby robbie » Fri May 18, 2007 7:40 am

Why is ms so different in virtually everyone? To different ends of the spectrum someone can be bedridden and some go through life with with mild sensory problems. What is it that decides that someone can have severe attacks with little recovery and some with severe attacks that recover pretty much 100%? What causes some to start out with R&R and some just go right into SP or PP ms. What is inside us that causes the decision to relapse or slowly get worse or in some to come once or twice and then not show up for years if at all. How can we all be so different but labeled with the same disease. My ms is slow but steady and when I sit and think I wonder what is inside of me doing this at it’s own pace and it’s own schedule, it’s like a monster running loose in a crowded place and he gets pissed off for what seems no reason at all and starts destroying whatever he can get his hands on.
There is probably no simple answer to this just like everything else with ms but any explanation would be great thx rob
Had ms for over 19 years now.
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Postby Lyon » Fri May 18, 2007 1:20 pm

Geez robbie, those are the questions that everyone would love to know. Knowing the correct answers to any or all of those questions would mean that we know a lot more about MS than we do now. In fact, knowing the answers to those questions would mean that we had a pretty good understanding of the disease.

If you're open to wild speculation, and it sounds like you are, it seems to me that the extreme variations found with MS cause some people to leap to the conclusion that MS in reality is several different diseases and that MS might turn into something else when it gets more advanced.

I think that's a bunch of hogwash which only seems a little credible due to our incomplete understanding of the MS disease process, the incomplete effectiveness of current medications and our currently necessary but misguided mindset that suppressing the entire immune system is an acceptible way to treat one aspect of the immune system which has gone awry.

The Tysabri "incident" points the finger more at the danger in our assumption that "more effective is better" when it comes to suppressing the immune system long term and actually has little or nothing to do with Tysabri being dangerous in itself.

I personally think that the most important lessons EVER learned about MS are being learned from Campath and high dose cyclosphosphamide as "rebooting" agents and from the Tovaxin trials.

The questions you ask are good, but there are some basics we're going to need to know first and I think the knowledge gained from Campath, HDC and Tovaxin are going to answer those basic questions.

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Postby robbie » Fri May 18, 2007 2:28 pm

Thx for your reply Bob, are the requirements for entering one of these trials very stringent, when I talked to my neuro about it she said it’s one of the only ways to help eliminate the natural course of ms variable in the research. Would you say then that the crabs are just a stepping stone to better treatments? Do you think in a way scientists know what direction to look i.e. Campath, stem cells but will exhaust the market of other drugs first? When I thought more about my questions I realized they weren’t very answerable. I am reading a book that says Parkinson’s has been around since the late 1700’s, back then called it the Shaking Palsy and you just give your head a shake to think where we are now and the answers to my questions are so foreign. Thx rob
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Postby Lyon » Fri May 18, 2007 3:58 pm

robbie wrote:are the requirements for entering one of these trials very stringent, when I talked to my neuro about it she said it’s one of the only ways to help eliminate the natural course of ms variable in the research.
Hi robbie,
Can you clarify the point your neuro was trying to make? What is she referring to when she says
it’s one of the only ways to help eliminate the natural course of ms variable in the research.
What is "it"?

robbie wrote: Would you say then that the crabs are just a stepping stone to better treatments?
I think you would have to call the crabs a stepping stone because they have filled the gap until something better comes along, but to be a stickler about semantics, I have it in mind that a stepping stone is a step in the right direction. In that regard the crabs don't fit the definition of stepping stone because future treatments, effective ones, are going to be a drastic departure from long term, broad based suppression, which is what every current MS treatment is based on. Only because of their proven danger are steroids and Novantrone not used longer term than they are.

Do you think in a way scientists know what direction to look i.e. Campath, stem cells but will exhaust the market of other drugs first?
Gosh, there are a huge number of researchers and it's impossible to say what they're thinking. I would hope that an increasing number are taking notice of the results from Campath, HDC and Tovaxin. I think any sensible researcher must realize that long term suppression can only take us so far....it obviously could never lead to a cure, but suppression has been the only available treatment strategy until just recently. We've all watched the percentages "game" with baited breath. The crabs=30%, Tysabri=65% (more or less) but the plain fact is that suppression could never lead to 100%.

Of course with a disease as hideous as MS ANY gain in percentage is awesome but then again, who wants to allow their MS progress to continue at 45% speed or even 10% speed? Slowing MS down in increasing degrees is not good enough with suppression because it's physically impossible to ever reach 100%.....well, killing the patient by suppression would achieve 100% but most people wouldn't find that an acceptible "cure".

Obviously pharmas are out to make money and I won't give them the benefit of the doubt regarding their good intentions but I don't believe in the conspiracy theory.....or at least I don't believe in the liklihood that they are powerful enough to quell something good.

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Postby robbie » Fri May 18, 2007 4:12 pm

I guess what i was trying to say was that when results of a trial are made some of that result must just rely on the fact that ms can on it's own come and go as it pleases.There must be a certain part of that 33% or 50% or what ever that is just the natural course of ms. She was saying by finding people with a more consistent relapse rate it helps this variable.
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Postby Lyon » Fri May 18, 2007 4:37 pm

robbie wrote:I guess what i was trying to say was that when results of a trial are made some of that result must just rely on thhe fact that ms can on it's own come and go as it pleases.There must be a certain part of that 33% or 50% or what ever that is just the natural course of ms. She was saying by finding people with a more consistent relapse rate it helps this variable.
Absolutely true. The reason for that is that in the past (not saying that things are entirely different now) MS treatments in trial have been shooting for a percentage of effectiveness. The people running the trial knew, or hoped, that their treatment would show some percentage of effectiveness and of course they want to show as high a percentage as possible.

What we are starting to see are some treatments which seem to be approaching 100% effectiveness and it seems that the trials are being held with equal amounts of cockiness and curiousity. Of course if you have a treatment that you feel is 100% effective you have the luxury of not caring what the course of the person's MS might have been because you are convinced that it's going to invariably stop dead in it's tracks. I think there are healthy signs that "what was" is not necessarily how things are always going to be.

Case in point http://clinicaltrials.gov/ct/show/NCT00296205?order=2

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Postby CureOrBust » Fri May 18, 2007 5:15 pm

Lyon wrote: ... The people running the trial knew, or hoped, that their treatment would show some percentage of effectiveness and of course they want to show as high a percentage as possible.

What we are starting to see are some treatments which seem to be approaching 100% effectiveness and it seems that the trials are being held with equal amounts of cockiness and curiousity. ...
Its a lot easier when they are defining the primary end points. ie If they know they dont help disability, it wont be an end point.
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Postby Lyon » Fri May 18, 2007 5:30 pm

CureOrBust wrote:Its a lot easier when they are defining the primary end points. ie If they know they dont help disability, it wont be an end point.
Hi Cure,
But that's a given. If ANY poor misguided person out there still directly associates stopping of the MS disease process with some mysterious dissolving of their disability.....that is an understandable misconception which has been generated by what we see in the relapsing/remitting phase. Some people will see great improvement when the disease stops. I dare say everyone will see some improvement but all of the improvement will stem from the body's ability to heal itself and not a bit can be attributed to the disease slinking off and dragging the disability off with it.

Decrease in disability is not a valid factor in attempting to determining the effectiveness of a treatment and I'm surprised that the people running the HDC phase II mentioned
The primary endpoint of this study is to evaluate the response rate of MS patients after high-dose cyclophosphamide therapy as determined by a sustained (greater than 6 months) decrease of greater than or equal to 1.0 in their EDSS score.


Either they are fools or they have already convinced themselves that when the disease is stopped most everyone can attain at least 1.0 drop in EDSS.

I'm not sure why :oops: but I've always liked this video http://tinyurl.com/33bshu
Bob
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MS research

Postby gwa » Sat May 19, 2007 7:03 am

robbie,

Shayk posted a link on the inflammatory thread that answers a lot of your questions posed on this thread. If you missed the link, here it is:

http://www.springerlink.com/content/q37 ... lltext.pdf

The main thing I got from reading the article is that no one has any concrete answers yet as to why the disease progresses differently in individual MS patients.

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infection

Postby Anecdote » Sat May 19, 2007 9:09 am

Robbie,

For many years, from the age of 24, my MS was very mild: The odd relapse which was never very disabling and rapidly cleared up leaving little in the way of deficits, I was still walking and cycling lots of miles during summer vacations and thought that I was going to be one of those people whose MS seemed never to get much worse. Then, in 2001, after a bad respiratory infection, I found myself hardly able to walk at all unaided and not far with help. Over a month or so, I improved somewhat, but the following year I still couldn't walk far, then I gradually began to get worse again.

I was eventually given a firm diagnosis of secondary progressive disease in 2003 and told there was nothing that could be done and I should look forward to a life of rapidly increasing disability. By this time I had lost the use of my right hand, my painting and violin repairing hand.

I gradually regained the use of this hand after starting treatment for chlamydophilus pneumoniae, my EDSS score dropped from a seven to a two over a couple of years and I have had no exacerbation of my MS since starting, so I guess that makes it plain what I think caused my disease.

Sarah
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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Postby CureOrBust » Sat May 19, 2007 4:48 pm

Lyon wrote:Decrease in disability is not a valid factor in attempting to determining the effectiveness of a treatment and I'm surprised that the people running the HDC phase II mentioned...
I disagree. It all depends on what you are trying to resolve. Fancy pictures from an MRI, or direct effects on someones day to day life. So far, most treatments only effected the fancy MRI images.

Also, there have been numerous studies that have compared two differing arms for progression of disability. This item will be most interesting when Tovaxin is released, if peoples EDSS still rises.
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Postby Lyon » Sat May 19, 2007 7:52 pm

CureOrBust wrote:
Lyon wrote:Decrease in disability is not a valid factor in attempting to determining the effectiveness of a treatment and I'm surprised that the people running the HDC phase II mentioned...
I disagree. It all depends on what you are trying to resolve. Fancy pictures from an MRI, or direct effects on someones day to day life. So far, most treatments only effected the fancy MRI images.
Hi Cure,
Without going into the argument of whether or not lesions and disability are directly correlated...the word disability, by definition, only refers to how the damage from the disease effects someone and doesn't specifically refer to MRI images or the status of inflammation or lesions.

With the limited effectiveness of current visualization techniques and the limited effectiveness of current MS treatments it's way too easy and it's detrimental to MS knowledge to fool ourselves into thinking that we can draw conclusions from the limited information that is available at this point.

CureOrBust wrote:Also, there have been numerous studies that have compared two differing arms for progression of disability. This item will be most interesting when Tovaxin is released, if peoples EDSS still rises.
I kind of think I understand what you're talking about regarding "compared two differing arms for progression of disability" but can you explain a little more clearly?

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Postby CureOrBust » Sun May 20, 2007 5:43 am

I think you misread me. I think we both know that there is no direct correspondence between MRI and dissability. Hence my point that a decrease in disability IS a valid measurement of treatment, as it measeures an almost independent result.

As for the "differing arms", over the past 12 months I know I have read numerous studies which have tried to compare treatments against placebo based on the progression up the EDSS (ie more disability) over a set period.

eg The placeebo group on average, progressed 1.2 points up the EDSS, while the treatment group only progressed 0.5 up the EDSS
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Postby TwistedHelix » Sun May 20, 2007 5:55 am

I tend to think that the key to why MS appears to vary so much lies in the unimaginable complexity of the human central nervous system. It's hard to think of a good way to illustrate this, but supposing you had 10,000 planet Earths, each with its own internet. On every planet, once a week, an explosion occurs at one completely random point on the network. The attacks never stop, but on many planets the sheer randomness means that only individual PCs are destroyed, or maybe local area networks; the flexibility of the web ensures that these losses can be worked around and recovered from, and are hardly noticed. On others, however, the servers and even power supplies are destroyed, until the accumulated damage becomes insurmountable.

In this analogy, the planets are the people with MS, the internet is the central nervous system, and the explosions are the continuing, underlying assaults which appear to be going on all the time in all kinds of MS. It's harsh, but if this model is true then it's just the luck of the draw which parts of the network become damaged, and which parts are "noticeable" in terms of symptoms.

MRI scans are useful to count the number of bomb sites, but it is their location which determines what effect it will have on the planet as a whole.

As for what causes the explosions in the first place, well, just like Planet Earth we seem to have a number of suspect terrorist groups, not all of them involved in every case.

I don't think I can stretch this analogy much further, except to say that, right now, I think I've had my own personal 9/11 slap-bang in the middle of my cerebral cortex!
Dom
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Postby Nemotoday » Sun May 20, 2007 6:22 am

Twisted Helix - A good analogy

Thanks
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