Crohn's Disease Forum » Books, Multimedia, Research & News » MAP Vaccine Ready for Human Trials - Could be Used for Crohn's


 
05-18-2014, 11:32 PM   #211
sir.clausin
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This is interesting, but if you believe Professor John Hermon-Taylor; then 95%ish of us with IBD harbors MAP; AND according to him MAP is this main infection and after that hell have broken loose, then other infections manifests like AIEC etc. So in other words, Crohn's is caused by a combination of infections and food allergies (which I heard from someone else) this apply to me, cause I get folliculitis and acne from almost everything I eat. For me who has my crohns isolated in the terminal ileum and have the most bizarre symptom picture, my biggest hope now is the vaccine from Qu biologics and then the anti-map therapy. I really hope that we find the answer soon, because I am sick and tired of this shit of disease.
05-19-2014, 07:00 AM   #212
sir.clausin
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Looks like cipro is only a temp fix, if it works.
http://journals.plos.org/plosone/art...l.pone.0022823

So in other words, the only hopefull treatment now is the Ssis vaccine from Qu.
05-27-2014, 04:59 PM   #213
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Stop talking and start donating!
05-27-2014, 05:04 PM   #214
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05-31-2014, 01:32 AM   #215
Malgrave
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Dr Behr's lectures on Crohn's, MAP and immunedeficiency:

2008 (parts 1-6):
http://m.youtube.com/watch?list=PL25...&v=nMucsxJau6k

2010 (parts 1-7):
http://m.youtube.com/watch?v=N8AYhnLkf9A

His list of publications:
http://www.mcgill.ca/molepi/publications
(Many of them concerning the link between MAP, Crohn's and immunedeficiency)

Update lecture from last week, hopefully available on youtube soon:
http://www.crohnsforum.com/showthread.php?t=63573
05-31-2014, 03:26 AM   #216
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Thanks for contributing Malgrave! Ive seen them before, did not know about he most recent lecture though.
05-31-2014, 10:36 AM   #217
kiny
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Dr Behr's lectures on Crohn's, MAP and immunedeficiency:

2008 (parts 1-6):
http://m.youtube.com/watch?list=PL25...&v=nMucsxJau6k
It sums up what many people think crohn's disease is. There is an innate immunedeficiency, a pathogen took advantage of the immunodeficiency and you get chronic inflammation until the bacteria is removed.

This theory is not the same theory as the theory about dysbiosis. This theory does not dismiss dysbiosis, it's there, but the dysbiosis is not behind the inflammation, it is a secondary event of the inflammation. People with intestinal tuberculosis show dysbiosis too.

All the candidate bacteria like MAP, AIEC, Campylobacter, Salmonella, Yersinia, Listeria....all intracellular, none are found in normal gut flora. If they are invlved things like fecal transplants would not help at all. (there are some strains of invasive E Coli in some healthy people, but don't have the same virulence factors).

For the first time in decades there is a new antibiotic against TB called bedaquiline, mycobacteria are notoriously hard to treat bacteria, almost all mycobacteria are pathogens and all of them are incredibly hard to kill.

The counterargument often used "If it was infection, why doesn't antibiocs cure it"....MAP is very resistant to antibiotics, and AIEC lives in biofilms, they're very resistant type of bacteria. MAP has the added problem that it is very slow dividing compared to TB.

Last edited by kiny; 05-31-2014 at 10:51 AM.
05-31-2014, 11:06 AM   #218
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Someone asked a question if you didn't eat meat you wouldn't get MAP etc. If Dr. Behr is right that the manure (sp?) infected with MAP is being thrown on fields, my guess is there are plants with MAP also.

edit: and it is, MAP in plants: http://www.ncbi.nlm.nih.gov/pubmed/21279514
05-31-2014, 12:02 PM   #219
Crohn2357
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I wonder if specific bacteriophages can be used againist MAP? If there is none or not known any right now, then maybe scientists will create it in the future. With genetic manipulations.
http://www.theguardian.com/world/201...-us-scientists
05-31-2014, 12:58 PM   #220
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Looks like cipro is only a temp fix, if it works.
...
So in other words, the only hopefull treatment now is the Ssis vaccine from Qu.
So what happened to John's vaccine has he given up if that is no longer a hopeful treatment to look to ?

Even if gut flora is not the cause i see no major harm in the attempt at this MAP theory. Unless there are unforeseen consequences of removing MAP from the digestive system.

From my own research i strongly believe a combination of a specific gene that affects how the immune system reacts to a bacteria or multiple bacteria is the cause.

This may even apply to other digestive disorders with different symptoms...theres no reason to suggest the immune system can only react in one way.
This is also why i believe Psoriasis is infact a bacterial cause with the immune system reacting to it. Theres many forms of psoriasis types which simply mean the immune system reacted a different way to the threat. It is also patchy in nature like Crohns. Sometimes i regard Crohns as the psoriasis of the digestive system.

The fact that there are differences between Crohn's and IBD could simply be the immune system's decision on how to best tackle a threat but fundamentally the cause is the same (not necessarily the same bacteria though).

The bigger question is, if it is MAP and vaccine does cure it, how likely is it to avoid MAP from your diet... its probably everywhere. I doubt highly the industry would have to change its methods because of this.
05-31-2014, 01:17 PM   #221
kiny
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Even if gut flora is not the cause i see no major harm in the attempt at this MAP theory. Unless there are unforeseen consequences of removing MAP from the digestive system.
Mycobacteria are intracellular, they're not found in gut flora. MAP is like intestinal TB, it resides in transmural tissue. How it enters the gut wall I don't really know, I know AIEC exploits things like peyer's patches.

The inflammatory response would start when MAP or any other bacteria comes into contact with the macrophages in the tissue. Infecting macrophages is what mycobacteria do, that is their forte.

The fact mycobacteria are extremely good at exploiting macrophages (just like AIEC) is why they're a good candidate for crohn's disease, because crohn's disease innate immunodeficiencies revolve around genes that affect macrophages.

If there is an expectation that people with ATG16L1 / NOD2 and IRGM mutations would be vulnerable to infection, the best candidates are mycobacteria and now also invasive E Coli.

And one of the places this would manifest itself is the intestine, since that's where the tissue is filled with macrophages.
05-31-2014, 01:26 PM   #222
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Mycobacteria are intracellular, they're not found in gut flora. MAP is like intestinal TB, it resides in transmural tissue. How it enters the gut wall I don't really know, I know AIEC exploits things like peyer's patches.

The inflammatory response would start when MAP or any other bacteria comes into contact with the macrophages in the tissue. Infecting macrophages is what mycobacteria do, that is their forte.
Hmm maybe micro tears from either poor diet (lack of fibre) or just genetic structure to begin with slowly and eventually leads to them entering into the gut wall.

The issue is what condition is the digestive system in before actually developing Crohn's, given there is no need to be checked to see the condition of the insides when we are symptom free we can't really know for sure. People only get tested after having symptoms. And i don't think a camera from a colonoscopy would see these microscopic tears anyway.
05-31-2014, 01:33 PM   #223
kiny
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The issue is what condition is the digestive system in before actually developing Crohn's
The earliest patients studies have inflamed lymphoid follicles. Invasive bacteria in the small intestine will come into contact with peyer's patches. The fact the peyer's patches are most active during teenage years and most people with crohn's disease develop it during teenage years I think are related.

Regarding route of transmission, MAP and AIEC could both be zoonotic. Cats actually carry AIEC, there are cats with "IBD".

If the cats are spreading around invasive E Coli, it would explain the weird studies that seem to make no sense, where a whole groups of people get sick with crohn's disease under the same roof, even though they can find no genetic susceptibility to CD.

Maybe someone should study the pets of people with CD.
05-31-2014, 01:43 PM   #224
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The earliest patients studies have inflamed lymphoid follicles. Invasive bacteria in the small intestine will come into contact with peyer's patches. The fact the peyer's patches are most active during teenage years and most people with crohn's disease develop it during teenage years I think are related.

Regarding route of transmission, MAP and AIEC could both be zoonotic. Cats actually carry AIEC, there are cats with "IBD".
I'm not sure what inflamed lymphoid follicles means, but if that allows invasion of the wall...is this the case for 100% of Crohn's patients, because it would seem more logical to find ways to prevent the invasive bacteria than finding a vaccine. As vaccine will only help until it may one day get into the wall again.
05-31-2014, 01:45 PM   #225
kiny
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I don't know, but I personally don't think you can single out a bacteria. Because people with immunodeficiencies (and people with CD have innate immunodeficiencies) are never susceptible to just one bacteria, it is always a plethora of infections they are vulnerable to.

But you can argue that some bacteria would be better suited at exploiting these deficiencies than others, and MAP and AIEC are extremely well suited at exploiting macrophages, that is what they do, that is how they survive.

If you actually find the bacteria within the tissue and granuloma, the gut flora theory starts to become an irrelevance. Maybe the dysbiosis helped AIEC proliferate, but that's irrelevant once it's in tissue, you're not going to remove the bacteria by trying to manipulate the gut flora, you could easily make matters worse.
05-31-2014, 01:52 PM   #226
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I don't know, but I personally don't think you can single out a bacteria. Because people with immunodeficiencies (and people with CD have innate immunodeficiencies) are never susceptible to just one bacteria, it is always a plethora of infections they are vulnerable to.

But you can argue that some bacteria would be better suited at exploiting these deficiencies than others, and MAP and AIEC are extremely well suited at exploiting macrophages, that is what they do, that is how they survive.
And so the theory is the vaccine provides patients with an ability to then fight it in future cases? Because if the vaccine doesn't make patients immune like the general population seem to be, then the vaccine is only a short term fix.

Then i wonder what does the immune system have in a healthy patient that a crohn's patient does not.
05-31-2014, 01:56 PM   #227
kiny
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Then i wonder what does the immune system have in a healthy patient that a crohn's patient does not.
"healthy" people don't have the autophagy and macrophage deficiencies. Many people without crohn's disease have CD predispostions in NOD2 and ATG16L1 too. There is an evolutionary reason why these mutations exist, maybe it protected us from a bacteria thousands of years ago, but now leaves us vulnerable to others.
05-31-2014, 02:01 PM   #228
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Another argument for MAP you could make is the overlap with Leprosy predisposition. The predispositions to crohn'd disease are extremely similar to the ones that leave you vulnerable to leprosy. NOD2 for example. We don't come into contact with leprosy, but my guess is we would be very vulnerable to it if we did.
05-31-2014, 02:10 PM   #229
Crohn2357
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kiny, what do you think about potential drugs targeting dna? For future?
05-31-2014, 02:18 PM   #230
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Don't know. I am not a fan of the recent advance in interleukin blockers. We sort of know what TNF-alpha does, there are many cytokine no one understands. I do not want people with crohn's disease to be an experiment platform. We need safer drugs.
05-31-2014, 02:19 PM   #231
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"healthy" people don't have the autophagy and macrophage deficiencies. Many people without crohn's disease have CD predispostions in NOD2 and ATG16L1 too. There is an evolutionary reason why these mutations exist, maybe it protected us from a bacteria thousands of years ago, but now leaves us vulnerable to others.
I don't suppose there is an actual way to solve these deficiencies in patients some how ?
05-31-2014, 02:22 PM   #232
kiny
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I don't suppose there is an actual way to solve these deficiencies in patients some how ?
There could be if you stimulate autophagy in cells, but autophagy has many other functions not related to bacteria.

Vitamin D is one of the ways autophagy might be stimulated because of NOD2 and VDR. AIEC is more susceptible if vitamin D status is optimal than if it is deficienct.

People with very low vitamin D status have worse crohn's disease.
05-31-2014, 02:24 PM   #233
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There could be if you stimulate autophagy in cells, but autophagy has many other functions not related to bacteria.

Vitamin D is one of the ways autophagy might be stimulated because of NOD2 and VDR. AIEC is more susceptible if vitamin D status is optimal than if it is deficienct.

People with very low vitamin D status have worse crohn's disease.
Hmm has there been much study in people who are first diagnosed with crohn's to already have been found to have low Vitamin D during the diagnostic stages?

But i don't think its as simple as this otherwise Vitamin D supplements would surely be solving the problem and i feel we would of found that out already.
05-31-2014, 02:27 PM   #234
kiny
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There have been, low vitamin D status is linked to worse crohn's disease.

Vitamin D also enhances macrophage function and helps kill AIEC. https://www.ecco-ibd.eu/publications...160coli-2.html

Vitamin D wouldn't help us rid of a bacteria directly, it would just help us overcome macrophage deficiencies, which would then allow us to better control pathogens exploiting those deficiencies.
05-31-2014, 02:33 PM   #235
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I see but making it worse is not the same as a potential cause.

Unless there are also studies to show it increases you chances in a substantial way.

Would someone with severe crohns perhaps need more than usual recommended Vit D amount per day for a while to control it ?

Because i don't buy into the "recommended daily intake" surely this is really is down to the individual person any may cause people to have less than they actual require.
05-31-2014, 02:35 PM   #236
kiny
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I agree, it is a number of factors probably, genetic and microbial. But low vitamin D status would leave you more susceptible, the fact Canada has one of the highest rates of crohn's disease and very little sunshine could be related.
05-31-2014, 02:36 PM   #237
Crohn2357
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So kiny, what are your thoughts about SSI treatment?
05-31-2014, 02:38 PM   #238
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I agree, it is a number of factors probably, genetic and microbial. But low vitamin D status would leave you more susceptible, the fact Canada has one of the highest rates of crohn's disease and very little sunshine could be related.
Doesn't Crohn's lower your ability to absorb Vit D? So its even more difficult at that point to keep levels up.
05-31-2014, 02:39 PM   #239
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Don't know much about it. Will read up on it if there is more info about it. Kind of hard to find info on what they are donig exactly. Some other ppl on the forum know more about it I think.
05-31-2014, 02:41 PM   #240
kiny
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Doesn't Crohn's lower your ability to absorb Vit D? So its even more difficult at that point to keep levels up.
Oral absorption? Not sure. But VDR polymorphism is linked to crohn's disease. It's a Vitamin D receptor.
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