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Cortene Peptide for MECFS? "Curative"?!

Ema

Senior Member
Messages
4,729
Location
Midwest USA
I think this is the peptide that Rich from ProHealth referred to on FB earlier in the year that caused such a stir. Maybe?

Anyone ever heard of it? Or the trial?

Science
Our science is based upon deep understanding of the corticotropin-releasing factor (CRF, also corticotropin-releasing hormone or CRH) system and its role in controlling the response to stress. The CRF system is comprised of 4 peptides, CRF and urocortins 1, 2 and 3, which bind to 2 receptors CRF1and CRF2(and splice variants thereof).
crf_sytem-new3.png


Internal or external stresses trigger the release of CRF from theHypothalamus, stimulating pituitary hormones to block non-essential function (thyroid and gonads) and causing theAdrenal glands (i.e., the HPA axis) to release cortisol, which coordinates the immune and metabolic response to stress. CRF also interacts with serotonin (5HT), which modulates norepinephrine and the autonomic system as well as other key neurotransmitters (GABA, glutamate, dopamine, acetylcholine, histamine) within the limbic system and forebrain, to modulate the behavioral response to stress.

Our research suggests that the upregulation of a single, stress-related receptor, CRF2, (in the raphe nuclei and limbic system of the brain) can explain the symptoms and anomalies of ME/CFS. Overstimulating this receptor induces many of the symptoms of ME/CFS in healthy animals, and we have developed a therapeutic candidate (CT38) that downregulates the receptor.

Having successfully completed a Phase 1 clinical trial (in healthy human subjects) under FDA oversight, we are planning to test CT38 in ME/CFS patients. We believe that a short course of treatment with CT38 may be curative.

http://corteneinc.com/mecfs
 
Messages
79
Location
Seattle
this looks like a moon shot to me, and, imo, the theory behind it makes sense at least superficially. i am very interested to see their early phase II results when they are available.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
The Cortene peptide normalizes calcium handling as well, according to some animal studies. I have a feeling that is part of the picture for us as well.
 

JES

Senior Member
Messages
1,320
CRF also interacts with serotonin (5HT), which modulates norepinephrine and the autonomic system as well as other key neurotransmitters (GABA, glutamate, dopamine, acetylcholine, histamine) within the limbic system and forebrain, to modulate the behavioral response to stress.

The above doesn't sound too different to me than how antidepressants work. Antidepressants modulate the stress response by blocking all kinds of receptors in the brain that are controlling serotonin, glutamate, norepinephrine, dopamine, etc. None of this has ever worked to treat/cure CFS/ME.
 

hixxy

Senior Member
Messages
1,229
Location
Australia
CRF also interacts with serotonin (5HT), which modulates norepinephrine and the autonomic system as well as other key neurotransmitters (GABA, glutamate, dopamine, acetylcholine, histamine) within the limbic system and forebrain, to modulate the behavioral response to stress.

@JES Note how it says also? It's obviously a secondary function and anti-depressants don't do the primary function.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
"CRH is at the heart of mast cell activation"

"CRH also increases TLR-4 (a significant source of inflammation)" (would explain LDN)

"Some studies suggest that CRH inhibits NK cell activity"

and more. Hmmmmm.

Selfhacked on CRH...
 

Martin aka paused||M.E.

Senior Member
Messages
2,291
I don't really get who they are. Kind of a startup? And what do they mean with "Overstimulating this receptor induces many of the symptoms of ME/CFS in healthy animals"...Which symptoms exactly? Is there a paper where I can read about this trial? I am a bit confused...

I would be interested in what Ron's team thinks about this approach...?!
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
So you can buy hairloss products that supposedly contain this peptide, astressin-b, which is a crf2 antagonist. But this blog says it is too heavy to be absorbed through the skin. I wonder how you know if that is true? @Hip?

This article seems to suggest it is just blocking expression in the skin? It's a total sales pitch though and it clearly didn't work all that well or it seems like we would have heard more about it since 2011.
 
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Ema

Senior Member
Messages
4,729
Location
Midwest USA
Where are the results of their Phase 1 Clinical Trial? Or animal trials for that matter?
I received a reply today to my inquiry stating that participant recruitment would begin in March 2018 in UT under a doctor there. The trial apparently requires living in UT for a number of months.

I have written back to ask about their earlier results and will let you know if I receive a response.
 

Hip

Senior Member
Messages
17,820
I read that intranasally compounds up to 2,000 daltons can be absorbed, but 4,000 daltons might be pushing it.
 

Hip

Senior Member
Messages
17,820
Whether this theory is correct time will tell, but the idea that the basic cause of ME/CFS is something as simple as the following hypothesis is very attractive:
the upregulation of a single, stress-related receptor, CRF2, (in the raphe nuclei and limbic system of the brain) can explain the symptoms and anomalies of ME/CFS.

We get so bogged down in all the myriad biological and symptomatic complexities of ME/CFS, but wouldn't it be nice if the whole damm caboodle could be explained by one single point of failure, like an abnormality in the expression of this corticotropin releasing factor receptor type II (CRF2).
 
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Hip

Senior Member
Messages
17,820
So you can buy hairloss products that supposedly contain this peptide, astressin-b, which is a crf2 antagonist.

It looks like from this paper that astressin-B is a non-selective CRF1 and CRF2 antagonist, and astressin2-B is a selective CRF2 antagonist. Since we would want to target CRF2, astressin2-B would be best, but the astressin-B found in hair loss products might suffice.

Astressin-B is found in the Spectral.F7 hair loss product, whose ingredients are:
Water, Glycerin, Propandiol, Lecithin, Phenoxyethanol, Caprylyl glycol, Glycine soja (soybean) oil, Octapeptide-2, Polysorbate 20, Astressin-B, Copper tripeptide-1, Disodium EDTA

But as discussed above, since the molecular weight of astressin-B is 4042 daltons, and both the human skin and blood-brain barrier have a 500 dalton limit to the molecules that can cross them, getting astressin-B into the brain is a problem.

It is possible that intranasal administration of astressin-B might work, because the intranasal route apparently bypasses the blood-brain barrier; but there is still around a 2,000 dalton limit for molecules crossing the nasal mucous membranes, so it would be a long shot if any astressin-B got through.


There are a couple of other CRF2 receptor antagonists listed here: antisauvagine-30 and K 41498, but they both have molecular weights in the 3,600 dalton region.
 
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hixxy

Senior Member
Messages
1,229
Location
Australia
We get so bogged down in all the myriad biological and symptomatic complexities of ME/CFS, but wouldn't it be nice if the whole damm caboodle could be explained by one single point of failure, like an abnormality in the expression of this corticotropin releasing factor receptor type II (CRF2).

It would be very nice indeed but I'm thinking that's going to be very unlikely. It seems more likely that even if this is involved it's only part of the story.