Trial of CT38 for ME/CFS by Cortene Inc.: big claims being made...

Sasha

Sasha

Senior Member (Voting Rights)
The claim that met my eye, on Cortene's website, was, 'We believe that a short course of treatment with CT38 may be curative.' OTOH, this seems to be some sort of commercial enterprise, being (I think) a drug company, or at least one that looks for uses for drugs (?), so maybe a bit of a pinch of salt to go with that.

Cort just started a series of three blog posts about this on Health Rising. There's info on Cortene's site, though (but not tons):

http://corteneinc.com/

The gist is:

Cortene said:
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.
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I'm a biomedical ignoramus. Anybody got any opinions? These guys seem to have come out of nowhere.

@Jonathan Edwards?
 
Their website doesn't even seem particularly coherent, much less indicate any plausible mechanism for a drug affecting the HPA axis to impact upon PEM, OI, muscular pain, etc. I think they're very unlikely to come up with anything useful when they're starting with implausible assumptions about the disease.

And with a complete lack of data thus far, this just looks like another sales pitch.
 
This sounds somewhat similar in concept to what Nancy Klimas has been talking about, i.e. flipping homeostasis back to normal in Gulf War Illness (and also in ME/CFS).

The treatment she is working on for GWI is a two step procedure where they first administer a drug to "block the proinflammatory cytokine cascade long enough to reduce neuro-inflammation [by 50%], and then block the HPA axis long enough to force it to do an internal reboot - a reset." She goes on to say,"If you did it in that time-course, 1 and then 2, [you could] hypothetically reboot the whole system back to normal."

This procedure has apparently restored GWI-induced animal models back to normal.

 
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I think its interesting. We've talked about ME being caused by faulty signaling mechanisms (either bad signals or receptors not working) so this looks to be along those lines. But I've no real idea about it. I assume they need some form of evidence before a trial which I assume comes from animals that they talk about.

I assume this is the receptor they are talking about
https://en.wikipedia.org/wiki/Corticotropin_releasing_hormone_receptor_2
 
Valentijn said:
Their website doesn't even seem particularly coherent, much less indicate any plausible mechanism for a drug affecting the HPA axis to impact upon PEM, OI, muscular pain, etc. I think they're very unlikely to come up with anything useful when they're starting with implausible assumptions about the disease.
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I believe it affects the HPA access but the also there are effects in the brain (Wiki mentions a alpha, beta and gamma type) so I think (but I really don't know what I am talking about!) there could be other effects as well a part from HPA

Wikipedia said:
CRHR2 beta is expressed in human brain; CRHR2 alpha predominates in peripheral tissues. The N-terminal signal peptides of corticotropin releasing hormone receptor 1 and CRHR2 beta are cleaved off in the endoplasmic reticulum to yield the mature receptors. In contrast, CRHR2 alpha contains a unique pseudo signal peptide that is not removed from the mature receptor. In adenylate cyclase activation assays, CRH-related peptides are 10 times more potent at stimulating CRHR2 beta than CRHR2 alpha and CRHR2 gamma, suggesting that the N-terminal sequence is involved in the ligand-receptor interaction.[9]
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Adrian said:
I believe it affects the HPA access but the also there are effects in the brain (Wiki mentions a alpha, beta and gamma type) so I think (but I really don't know what I am talking about!) there could be other effects as well a part from HPA
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As far as I can tell, the gene is only expressed in the brain. So a drug targeting it would be acting in a purely central manner - which only cures the disease if there's no peripheral pathology.
 
Valentijn said:
As far as I can tell, the gene is only expressed in the brain. So a drug targeting it would be acting in a purely central manner - which only cures the disease if there's no peripheral pathology.
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There could be a signalling storm where some signals in the brain disrupt a process and lead to other signals being sent out into the body to control metabolic processes etc. I've often thought of ME as a control system failure where there are lots of dynamic loops with one breaking and then leading to knock on effects on other loops. But from my part its all speculation because I don't understand the biology (I can see it from the idea of modelling a system where a disruption on one part leads to other linked systems being affected).

[Adding]
If there was a hibernate state (or the one being proposed by Naviaux) then I assume in animals where this state is useful there will be some sort of triggering process that leads to the other processes so does this suggest there could be a pathway from some distant evolutionary time.
 
Simon M said:
Like @Valentijn I am unimpressed without some published data to back it up. There are no end of plausible hypotheses out there and almost every one of them will be wrong.
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I'm especially skeptical of hypotheses which have been beaten to death, such as the HPA axis and central dysfunction, which are both being combined by this group. It doesn't help that their "Science" intro sounds over-simplistic ... and I certainly haven't seen them demonstrating a "deep understanding" of it:
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.
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Like most HPA and central sensitization theories, their theory is all about (psychological) stress:
Internal or external stresses trigger the release of CRF from the Hypothalamus, stimulating Pituitary hormones to block non-essential function (thyroid and gonads) and causing the Adrenal 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.
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Their theory is that the gene is upregulated in the brain:
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.
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CRF1 and CRH antagonists have been shown to reduce stress, anxiety, and associated behavioral problems in animal trials. While CRH can have some interesting biological effects, those are primarily due to activity outside of the brain. Whereas the CRH receptor being targeted by this group is only in the brain. Frankly, I don't see any plausible explanation for how it could impact PEM, muscle twitches, muscle pain, etc, so it seems to be yet another case of treating ME/CFS as a chronic stress/sensitization response.

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.
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Why has it apparently not been published?

We believe that a short course of treatment with CT38 may be curative.
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What's the basis of that belief, beyond the belief that one receptor could cause ME/CFS somehow? How is this hypothesis involving this receptor superior to the hundreds of other receptors or other proteins which could account for some ME/CFS symptoms?

Their CMO is Dr Hunter Gillies, listed as a practitioner of Tim Noake's low-carb nutritional advice. Noakes explicitly believes that chronic fatigue is the result of the brain mistakenly believing that the body is fatigued and needs to rest. I'm concerned that Dr Gillies shares the same belief, and their line of research would suggest that he does.
 
Forbin said:
This sounds somewhat similar in concept to what Nancy Klimas has been talking about, i.e. flipping homeostasis back to normal in Gulf War Illness (and also in ME/CFS).

The treatment she is working on for GWI is a two step procedure where they first administer a drug to "block the proinflammatory cytokine cascade long enough to reduce neuro-inflammation [by 50%], and then block the HPA axis long enough to force it to do an internal reboot - a reset." She goes on to say,"If you did it in that time-course, 1 and then 2, [you could] hypothetically reboot the whole system back to normal."

This procedure has apparently restored GWI-induced animal models back to normal.

Click to expand...

Thanks for posting Dr Klimas. What is the name of the medication she says was given? Couldn't understand her.
 
Isn't it fairly well established that the HPA axis in ME/CFS is nearly normal, while the impact of the illness is typically devastating? It just doesn't seem to add up. I agree that ME/CFS involves stress/exertion/danger/bad stuff hypersensitivity but it seems to involve different pathways/systems than the HPA axis.

The kind of sensitivity (in my case) seems to be different than what's ascribed to HPA axis stuff. I have considerably higher tollerance for emotional stress than for ordinary working and walking for example. I think you can even see this in the patient community that has major limitations doing ordinary daily activities but can (generally) bear quite a bit of stress related to things like the PACE trial or the hopelessness of the situation etc.

Am I missing something?
 
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I find their list of illnesses interesting, IBS, atypical depression, fibromyalgia, ME/CFS and other diseases. Promote a product they plan to get FDA approval on on a blog. Reminds of that "drug" that was for ME/CFS, Parkinsons and a few others that was a collection of supplements (and herbs?) not too long ago.
$5 says the goal is to spin the flimsiest evidence they can, get FDA approval and milk it for all the money they can get away with. And since quite a few things can give us a short boost its not undoable but its still likely a sham.
 
Alvin said:
I find their list of illnesses interesting, IBS, atypical depression, fibromyalgia, ME/CFS and other diseases. Promote a product they plan to get FDA approval on on a blog. Reminds of that "drug" that was for ME/CFS, Parkinsons and a few others that was a collection of supplements (and herbs?) not too long ago.
$5 says the goal is to spin the flimsiest evidence they can, get FDA approval and milk it for all the money they can get away with. And since quite a few things can give us a short boost its not undoable but its still likely a sham.
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This is why we still need the researchers to keep working. This is a drug that was developed and is now seeking a home. They did not study ME/CFS, determine a coherent model of disease, and then select a candidate therapeutic. But then again, maybe it will have some merit. Suramin is a long-shot too. Hopefully any trial will teach us something and perhaps get other pharmaceuticals interested.
 
Diwi9 said:
This is a drug that was developed and is now seeking a home. They did not study ME/CFS, determine a coherent model of disease, and then select a candidate therapeutic. But then again, maybe it will have some merit.

Hopefully any trial will teach us something and perhaps get other pharmaceuticals interested.
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Cool, so i can try to spin supplements or snake oil, cast a wide net with pseudo scientific explanations and people will be happy with all the good i am doing.
 
Perrier said:
Thanks for posting Dr Klimas. What is the name of the medication she says was given? Couldn't understand her.
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In the video, she is actually talking about a two step protocol that, hypothetically, could treat Gulf War Illness. I would assume that their protocol for ME/CFS would be different in some way, i.e. other drugs, or different number of steps, timing, etc...

The only drug she mentions in the video for treating Gulf War Illness (in their animal model) seems to be the one that would "block" the HPA axis, the second step in that protocol. In that context, she mentions mifepristone, which is actually the abortion drug RU-486. According to Wikipedia, one of the properties of RU-486 is that it "antagonizes cortisol action competitively at the receptor level."

Again, this is in a Gulf War Illness animal model, so it could well be completely irrelevant (or dangerous) in regard to any kind of treatment for ME/CFS in humans.
 
Forbin said:
In the video, she is actually talking about a two step protocol that, hypothetically, could treat Gulf War Illness. I would assume that their protocol for ME/CFS would be different in some way, i.e. other drugs, or different number of steps, timing, etc...

The only drug she mentions in the video for treating Gulf War Illness (in their animal model) seems to be the one that would "block" the HPA axis, the second step in that protocol. In that context, she mentions mifepristone, which is actually the abortion drug RU-486. According to Wikipedia, one of the properties of RU-486 is that it "antagonizes cortisol action competitively at the receptor level."

Again, this is in a Gulf War Illness animal model, so it could well be completely irrelevant (or dangerous) in regard to any kind of treatment for ME/CFS in humans.
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Dear Forbin
I do appreciate your detailed response. I saw another interview with Dr Klimas (can't find it anymore) where she is suggesting that there are enough similarities between Gulf War Illness and ME for her to consider using the GWI protocol on ME patients, at some point in a trial, if things work out in the present trial.
 
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