Top line results from Redhill's Triple Antibiotic for MAP study

It is controversial but perhaps they go into a L phase or persistent phase where no amount
or type of antibiotic will kill. The trial dose schedule might be wrong, once a week or so to
have them revert to normal, then kill again with antibiotics. Repeat the cycle for as long as it takes.

here is something on lyme.

oldmike

/www.holtorfmed.com/are-lyme-patients-being-dosed-incorrectly/

More from John Aitken: /humanpara.org/map-blood-culture-and-diagnostic-testing/

I hope they adress this problem in the trial paper. When a Crohn's patient sends blood samples to John Aitken's lab, in addition to looking for different forms (Large, small, ruptured, daughter), he looks for the number of persister form MAP in the blood and sends that information as a report to the patient.

Hopefully the researchers in the RHB-104 trial has done the same and add those data into the trial paper that will be published - so that we can see them, and maybe find a correlation between the patients' health status, the treatment's effects, and the microbial data.

Post Edited (xy123) : 8/8/2018 2:35:07 PM (GMT-6)

Thanks OM.

I find it kind of interesting that people (GI's, Researchers etc) have no problem accepting 'dormant' forms of bacteria and the problems that can occur along with the difficulty in treating them in diseases like tuberculosis, etc. - yet when the MAP specific researchers are trying to tell them this is what they think the issue is in Crohn's and maybe IBD in general (dormant forms of MAP) they are labeled 'fringe researchers' or worse...

1 in 3 worldwide will test positive for dormant tuberculosis. Heck, someone in the Crohn's section just posted about testing positive a few weeks ago as they have to now undergo abx treatment for TB. A couple of other people have also posted about the issue over the last year I believe.

---------

Here is the abx testing of RHB-104 against mycobacteria versus the traditional 3 separate antibiotics.
/www.ncbi.nlm.nih.gov/pmc/articles/PMC4908774/

- it's pretty long. The idea being that the three abx combined together and taken all at once seems to be a little more effective than taking the individual doses. Also lower doses are seemingly required.

But they seem to know that they do not get rid of all the bacteria in the samples they take during treatment - "does not fully eradicate the bacteria" as they keep saying. That is why they say it is an 'indefinite' amount of time on the abx. But they seem fairly confident that a reduction in the number of bacteria corresponds with a reduction in symptoms.

Personally I don't like the idea of being on abx 'indefinitely'. But if I were to flare again sometime I think I might try versus biologics. Not sure. Or I would wait until I was uot of options and facing losing my colon perhaps.

---------

As for the dormant forms (persisters) they know metronidazole (Flagyl) work against them, but here is what is said about it: However I believe Dr. Borody still uses it along with other abx in non-responders until he get's a combination that works for that patient. My understanding is he starts with the triple abx and adds to it if they are not responding.

"Many patients also have previous exposure to metronidazole (Flagyl). What is little known is that Metronidazole has activity against dormant forms of mycobacteria 1,2. Many patients with Crohn's have been exposed previously to Flagyl, and there is a remote possibility that pre-treatment in the past with Metronidazole may make Mycobacterium avium subspecies paratuberculosis infections more difficult to eradicate. This is speculation, but needs to be kept in mind.

1 Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis.
Wayne LG, Sramek HA.

2 Oxygen depletion induced dormancy in Mycobacterium smegmatis.
Dick T, Lee BH, Murugasu-Oei B.

Canada Mark said...
Thanks OM.

I find it kind of interesting that people (GI's, Researchers etc) have no problem accepting 'dormant' forms of bacteria and the problems that can occur along with the difficulty in treating them in diseases like tuberculosis, etc. - yet when the MAP specific researchers are trying to tell them this is what they think the issue is in Crohn's and maybe IBD in general (dormant forms of MAP) they are labeled 'fringe researchers' or worse...

The term IBD is a misnomer and should not be used in any medical/scientific context because its use is adding to the misunderstanding of these two diseases in my opinion. UC seems more like an autoimmune disease (Disease restricted to colon, whole segment is involved [say, whole sigmoid colon] rather than patchy involvement, and mucosal inflammation) while CD seems more like a persistent infection due to the immune system not being able to clear the infectious agents (transmural inflammation, patchy inflammation [bacterial clusters?], granulomas, whole digestive system [and even skin (1) and theoretically all parts of the body] is involved, antibiotics are effective, genetic predispositions that are related to the immune system's handling of intracellular bacteria (2)(3), defective autophagy, the findings which show high prevalence of intracellular bacteria in Crohn's patients' tissues and blood [compared to UC patients and the general population], Koch's postulates have been met for MAP(4)). The aetiology and pathogenesis of UC and CD are highly distinct from each other. The only things they share are colonic inflammation, some of the treatments used, and colorectal surgery when needed. By the way, immunosuppressants have been used in the past to treat TB, because the Mycobacterium tuberculosis doesn't kill you - the inflammation does.

No one theoretically expects the anti-MAP therapies (be it the antibiotics or vaccines) to positively affect the course of UC in majority of cases.

In theory, there is at least one persistent infection (be it MAP, AIEC or another intracellular pathogen) in Crohn's patients which exploits the host immunodeficiency and the immune activation against it starts the cascade of inflammation that never stops. Basically the immune system attacks; but cannot eradicate the pathogen, and the immune activity/inflammation never stops.

(1): This was first reported in 1976 by Segal et al.
Neutrophil Dysfunction In Crohn's Disease
http://www.thelancet.com/journals/lancet/article/piis0140-6736(76)91024-2/abstract

(2): VIEW IMAGE (till 2012)

(3): Crohn's as an immune deficiency: from apparent paradox to evolving paradigm.
https://www.ncbi.nlm.nih.gov/pubmed/23256761

Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease
http://jem.rupress.org/content/206/9/1883.full

Revisiting Crohn's disease as a primary immunodeficiency of macrophages
http://jem.rupress.org/content/206/9/1839.full

Is Crohn’s disease due to defective immunity?
http://gut.bmj.com/content/56/1/2?ijkey=eb8a8854e00027337f2e2a3173ce65be17d31bd0&keytype2=tf_ipsecsha

Defective acute inflammation in Crohn's disease: a clinical investigation
http://www.thelancet.com/journals/lancet/article/piis0140-6736(06)68265-2/fulltext

Vitamin D, NOD2, autophagy and Crohn’s disease
http://www.tandfonline.com/doi/full/10.1586/eci.10.31

Abnormalities in the handling of intracellular bacteria in Crohn's disease: a link between infectious etiology and host genetic susceptibility.
https://link.springer.com/article/10.1007%2Fs00005-008-0026-1

Crohn’s disease as an immunodeficiency
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4618314/

Defective innate immunity in inflammatory bowel disease: a Crohn's disease exclusivity?
https://insights.ovid.com/pubmed?pmid=21483259

Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease.
https://www.ncbi.nlm.nih.gov/pubmed/10877227

Crohn's disease: an immune deficiency state.
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4568313/

Integrating theories of the etiology of Crohn's disease. On the etiology of Crohn's disease: questioning the hypotheses.
https://www.medscimonit.com/download/index/idart/445257

The immunopathogenesis of Crohn’s disease: a three-stage model
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4529487/

Mycobacteria in Crohn's disease: A persistent hypothesis
https://academic.oup.com/ibdjournal/article-abstract/12/10/1000/4682863?redirectedfrom=fulltext

Mycobacteria in Crohn’s disease: how innate immune deficiency may result in chronic inflammation
https://www.tandfonline.com/doi/full/10.1586/eci.10.29

(4):

kiny said...
Don't remember what study it was, but if you take human MAP antigen, from people with crohn's disease, and infect goats with it, the goat will develop johne's disease.

Another crohnsforum.com member said...
Kiny you may be referring to Koch's postulates fulfilled establishing MAP as a causal agent of Crohn's Disease in Chiodini study:

Van Kruiningen, H.J., Chiodini, R.J., Thayer, W.R., et al. (1986) Experimental disease in infant goats induced by a Mycobacterium isolated from a patient with Crohn’s Disease. A preliminary report. Digestive Diseases and Sciences, 31, 1351-1360.

From: https://www.crohnsforum.com/showthread.php?t=39393

Dr. Borody also asserts that Koch’s postulates have been met in this interview: https://www.youtube.com/watch?v=crm4pkz6x2m

Koch's postulates: https://en.wikipedia.org/wiki/koch%27s_postulates

Canada Mark said...
Here is the abx testing of RHB-104 against mycobacteria versus the traditional 3 separate antibiotics.
/www.ncbi.nlm.nih.gov/pmc/articles/PMC4908774/

- it's pretty long. The idea being that the three abx combined together and taken all at once seems to be a little more effective than taking the individual doses. Also lower doses are seemingly required.

But they seem to know that they do not get rid of all the bacteria in the samples they take during treatment - "does not fully eradicate the bacteria" as they keep saying. That is why they say it is an 'indefinite' amount of time on the abx. But they seem fairly confident that a reduction in the number of bacteria corresponds with a reduction in symptoms.

Personally I don't like the idea of being on abx 'indefinitely'. But if I were to flare again sometime I think I might try versus biologics. Not sure. Or I would wait until I was uot of options and facing losing my colon perhaps.

A few months ago I researched the antimycobacterials' effects on Mycobacterium avium complex (MAC). Read many studies with different antimycobacterial agents with different combinations and different doses. In the end, I thought to myself that the doctors (they are John Taylor, Borody, Naser I guess) who have created the current anti-MAP antibiotics (Clarithromycin, clofazimine, and rifabutin) plan have done a good job because from my research I realized that this combination has a good synergetic effect (increased effectiveness, decreases the doses needed) and it has a better side effect profile and more effective than others[singular or other combinations]).

Post Edited (xy123) : 12/7/2018 9:06:38 AM (GMT-7)