Replies to post #201089 on Innovation Pharmaceuticals Inc (IPIX)

[To infinity and beyond!]

agree of course hard to know exactly what major response will be in the gut to B, and at what levels different actions will predominate. maybe 100 fold, 1000 fold variation in killing E Coli vs pde4 inhibition vs other effect, who knows-

Not saying in any way it won't be just fine, just something to keep in mind

[slcimmuno]

good to see you posting again biodoc -- need more of us Science Geeks on the Board reminding folks of the IPIX There There.

the Gut Micribiome -- dysbiosis vs homeostasis -- is complicated.

just came across this article that suggests inflammation comes first in IBD pathogenesis. lucky B is such a broad spectrum drug as to MOA, pulling many beneficial therapeutic levers.

btw, .71c on the day ---- and who were those saying the PR was fluff?

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Dysbiosis in Crohn's disease - Joint action of stochastic injuries and focal inflammation in the gut (Jan 17)

Gut homeostasis involves interrelated biological networks that include the immune system, specialized cells of the epithelium, such as Paneth and goblet cells, as well as triggers derived from the microbiota. Disruption of these homeostatic interactions may lead to the pathogenesis of inflammatory bowel diseases (IBD). To develop more targeted and individual treatments in Crohn's disease and ulcerative colitis, it becomes more and more important to link key mechanisms of the disease pathogenesis to distinct IBD subsets. For the first time, our laboratory demonstrated a causal role of the microbiota for the development of Crohn's disease (CD)-like ileitis, supporting the hypothesis that a non-infectious, dysbiotic microbial ecosystem harbors aggressive traits relevant for the induction of chronic inflammation in the disease-susceptible host (i.e. TNF?ARE mouse model). Despite a growing body of evidence claiming a primary role for Paneth cells in the pathogenesis of ileal CD, we showed in the TNF?ARE mouse model that Paneth cell failure or exhaustion is a secondary event to inflammation. Therefore, additional mechanisms may act synergistically to initialize the development of CD-like pathology. Hereby, we propose a novel hypothesis suggesting that individual development of dysbiotic communities is based on stochastic injury and focal inflammation of the epithelial lining that propagate radially, finally leading to an aggressive microbial milieu.

http://www.tandfonline.com/doi/abs/10.1080/19490976.2016.1270810

[MinnieM]

Interesting... thanks...

I'm looking forward to seeing the topline brilacidin ph2 Oral Mucositis results that are coming soon. ;)





In Reply to 'biodoc'
A couple thoughts. First, the gut concentrations for anti-inflammatory, immunomodulatory and wound healing effects of Brilacidin may be lower than the MIC for E. coli. As you know, Brilacidin is predominantly for gram positive organisms with modest gram negative coverage. My recollection is that E. coli had a higher MIC than the gram positives studied. I'm sure IPIX has a sense for the potential cidal effect on the gut biome and has a read on the concentrations necessary for anti-inflammatory, immunomodulatory and wound healing effects. Also, as I believe we will see from top line B-OM, it doesn't take long-term continuous Brilacidin exposure for an anti-inflammatory response.