Cure said
The tissue in the brain is very different from that found around leg ulcers. Specifically with my limited knowledge, nerves themselves; brain mylinated by oligodendrocytes, peripheral by schwann.
I agree! I just wondered if it had been tried at all.........apparently not!
I'd like to expand on an idea in one of my posts above by adding info from another thread I wrote so it is here regarding how/why immue suppression might seem to work if Zamboni is right. My mind has been turning this over a lot because obviously it looks like it helps to knock it out. Why might that be?
here's that list again on slide 4 of the Zamboni presentation Cure linked. It is a list of inflammatory factors known to be present in MS lesions and also in venouos ulcers:
Table 1 Common findings of the inflammatory chain in CVD and MS
Finding CVD References Multiple sclerosis References
Altered venous haemodynamics
Perivenous inflammation
erythrocyte extra-vasation
Haemosiderin deposits
Adhesion molecules and white cells activation
Macrophage migration-infiltration
T cell migration-infiltration
Iron laden-macrophage
MMPs hyper-activation
TIMPs hypo-expression
Local iron overload
Urine haemosiderin test
HFE mutation
Fibrin cuff (on going reparative process)
Note about the chart: : you see that everything that is listed is known to be true of venous ulcers AND MS lesions, in the real chart, which I was unable to paste in, there are references for each and every one of those things; it's not like Zamboni is making this theory from now where, it comes from known research. The only thing not known is the first; the altered haemodynamics. THAT's what his research on those 750 people set out to show. IMHO, he showed it well.
They have, of course, now had roughly 750 people go through the clinic in 3 blinded controlled research studies and it turned out that all the people with MS had reflux and abnormal doppler readings in 2 or more findings where the other people, whether they had other neurological disease or other vascular or disease or were older normal people, had no more than one abnormal reading
This is to me the most exciting new research along the MS lines to come along in a long time: it's novel and a completely new direction for research.
People who've been in the autoimmune camp find the whole notion hard to get their minds around, the biggest question being
'Yeah, but why does revimmune/campath/tysabri etc work? He can't be right.'
Look at that chart /list, those things will be impacted by knocking out the immune system because they are all inflammatory markers dependant on immune activation to happen, that's likely why it seems to help to knock out the immune system. Some of the damage is caused by these inflammatory markers.
That should not be new ideas to anyone, that's what they've been telling us for years; the inflammation itself is causing the damage. What they have not recognized is that this inflammation may be SECONDARY to a mechanical damage in the first place, according to Z, caused by reflux.
For example; by what measure do they go around telling us that "revimmune worked"?
PRIMARILY because the main criteria they use for "did it work" is whether or not new inflammation and GD enhancement shows up, well, when the immune system has been hamstrung it can't do that even if it wants to/needs to when degeneration is happening in that area.
To offer the idea that something like ASCT which severely suppresses immune function does NOT "stop MS damage" as is often said, I will add a chunk from another paper on autologous stem cell transplants that shows that after such treatments when the patient's immune system has been completely wiped out, people STILL show degeneration of brain tissue even though the inflammation is gone. This comment is from a pathologist who austopsied brain tissue after people died post ASCT:
Autopsy samples from these patients revealed that in
all cases there was an almost complete absence of inflammatory
markers in the brain, notably of T cells. On
the other hand, there was significant staining for amyloid
precursor protein (APP) inclusions, a marker of
acute axonal damage (Fig. 5). This suggested that even
though inflammation had been abolished, neurodegeneration
was still proceeding in the brains of these patients,
and thus that neurodegeneration was not a direct
consequence, at least in the short-term,of inflammatory
damage to the nervous system.
from Wolfgang Bruck "Inflammatory Demyelination is not central to the pathogenesis of multiple sclerosis" (I own a copy)
Could the reason for the ongoing degenerative damage in brain be that the mechanical damage of reflux has been ignored? Are these immune treatments kicking all those immune factors out of the lesion, until the next time there is a big dose of reflux to cause new damage and new invitation to the immune system to come in and clean up?
Is that why some people do better for a while after immune suppression then reactivate: mechanical damage sets the stage for a whole new round of immune activation?
I don't know the answer but these speculations might be an explanation for how Zamboni can be right even though it "seems" like severe immune suppression helps MS.
One thing is true, there is a fair body of research like the Bruck bit I added a paragraph from that makes a reasoned and supported case for the idea that MS is primarily degenerative not autoimmune, but that having been said it may be possible that the eventual "best" treatment includes some form of immune suppression AS WELL AS vascular repair.
What will make the difference is whether or not there is some compartmentalization (locking into the brain behind the BBB) of some of these inflammatory factors and possibly a need to control them somehow after the fact.
OTOH stroke survivors do not need lifetime immune suppression so maybe not.
More work will need to be done before the eventual best management of this issue is known, but one thing is sure, addressing the reflux, assuming it turns out to be pathognomic for MS, will be critical irf we want to stop progression.