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Cortene Peptide for MECFS? "Curative"?!

junkcrap50

Senior Member
Messages
1,328
Also, Urocortin II is a 38 amino-acid peptide.

Urocortin II is essentially an anxiolytic (anti-anxiety), an anorexigenic (appetite suppressant) and a hypotensive (blood pressure reducer.)

If CT38 is indeed Urocortin II (or an analog), what are the odds that this is curative for SEID?

What's the big deal if it is Urocortin II? I don't understand the significance. Has Urocortin II already been studied? Tried on CFS? What's the significance of Urocortin II and it being Cortene 38?
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
Quoting the blog:
The animals’ heart rate increases, their blood pressure, body temperature and gut motility are reduced, their urine production is affected, their movement is dramatically reduced, and their stress hormones are released (norepinephrine and cortisone, the rat equivalent of cortisol).
I'm a bit troubled as these are not universal symptoms and in fact many of us don't fit this profile very well. While many patients have high levels of norepinephrine (I am the opposite), I think most have low cortisol--at least in the morning. And many of us have low heart rates except in the cases of POTS patients where the HR jumps in response to standing, whether or not it was low while sitting or reclined. They don't indicate "how" urine production is affected but that would be interesting to know as some of us know that our urine production is higher than normal. There has been a lot of discussion as to whether we have diabetes insipidus as part of our profile.
 

Mary

Moderator Resource
Messages
17,321
Location
Southern California
Cortene posits that elevated levels of serotonin are responsible for many/most ME/CFS symptoms, and their proposed treatment is a 38-amino acid peptide. I'm wondering how, if at all, this would relate to this article: http://www.ncf-net.org/forum/Fword.htm which talks about elevated levels of tryptophan (which is needed to synthesize serotonin) causing something called "central fatigue" and how a remedy for central fatigue is BCAAs. The article also mentions a compound called BCH which is supposed to accomplish the same thing.

The implications are important because the fatigue in CFS is central fatigue, in other words, fatigue in the central nervous system (CNS)! According to these researchers, fatigue in the CNS results from fatigue that occurs in a large portion of intercerebral control circuits caused by suppression in the level of voluntary exciting, which are suppressed in the number of motor units to the level of voluntary neuromuscular junction - muscle fibers and the firing frequency. In other words, CFS fatigue is a fatigue different from the fatigue in the motile muscles themselves. Moreover, these researchers have found that this fatigue is different from the so called tiredness feeling caused by physical (muscular) fatigue and, in fact, is generated in a state that is not accompanied by physical fatigue.

Any ideas you brilliant scientists out there (which I am most definitely not!)? @Hip? Also, I saw an older post of yours recently where you tried leucine and said it didn't help you. It might be worth a try to take the full complement of BCAAs, including valine and isoleucine, as well as leucine.

I've posted several times about BCAAs and how they cut my PEM recovery dramatically; but unfortunately they don't prevent PEM from occurring to begin with.
 
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Ema

Senior Member
Messages
4,729
Location
Midwest USA
Cortene posits that elevated levels of serotonin are responsible for many/most ME/CFS symptoms, and their proposed treatment is a 38-amino acid peptide. I'm wondering how, if at all, this would relate to this article: http://www.ncf-net.org/forum/Fword.htm which talks about elevated levels of tryptophan (which is needed to synthesize serotonin) causing something called "central fatigue" and how a remedy for central fatigue is BCAAs. The article also mentions a compound called BCH which is supposed to accomplish the same thing.
.
BCH is 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid.
 

Hopeful1976

Senior Member
Messages
345
Who is hopeful?
I want to be, but i am equally very scared to be... I dare not allow myself to think too much about - it is my/our finest dream to be well again. Such a gift it would be. But also devastating if i invest too much hope. It's awful how this illness makes cynics of us. Cynics with a secret hope deep inside all of us though.
I would love to know what Ron and the omf thinks of it.
 

Cort

Phoenix Rising Founder
Quoting the blog:I'm a bit troubled as these are not universal symptoms and in fact many of us don't fit this profile very well. While many patients have high levels of norepinephrine (I am the opposite), I think most have low cortisol--at least in the morning. And many of us have low heart rates except in the cases of POTS patients where the HR jumps in response to standing, whether or not it was low while sitting or reclined. They don't indicate "how" urine production is affected but that would be interesting to know as some of us know that our urine production is higher than normal. There has been a lot of discussion as to whether we have diabetes insipidus as part of our profile.
The heart rate situation is complicated - my understanding is that we have higher than normal heart rates during sleep and at rest and lower than normal heart rates during exercise (chronotropic incompetence).

I believe Cortene believes that higher cortisol earlier in the disease lead to lower cortisol later.

Because the initial jolt or trauma or infection or whatever may over turn into something else over time I don't know how clearly it should reflect ME/CFS. The idea that there's high cortisol early in the disease and low cortisol later has been floating around for quite some time. I don't think it's ever been tested though. It would be fascinating to find out.

CT38 is a big experiment. It's a very interesting and totally untried hypothesis and drug. I don't have a clue how it will turn out.
 
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Cort

Phoenix Rising Founder
I want to be, but i am equally very scared to be... I dare not allow myself to think too much about - it is my/our finest dream to be well again. Such a gift it would be. But also devastating if i invest too much hope. It's awful how this illness makes cynics of us. Cynics with a secret hope deep inside all of us though.
I would love to know what Ron and the omf thinks of it.
I think maybe cautious hope is appropriate. I keep coming back to Ron Davis's comment about how complex the body is. It's dauntingly complex and plenty of time drugs that seem like they should work don't. I think it would take a bit of luck for a new drug based on a hypothesis to works AND it's certainly possible that it will,.

These guys do seem to be real sharp! If they think it has a good enough chance to spend a couple of years working on it full time, that's pretty good.

There's some animal data and some human data but it's limited; the drug is not being used in humans - so we don't have data there - and it's certainly never been applied to someone with ME/CFS. I think its experimental in the true sense of the word. Crossing fingers time :)
 
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Cort

Phoenix Rising Founder
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.
I think there are some big differences. Antidepressants can have a very wide mode of action while Cortene is much more targeted. Plus SSRI's attempt to boost serotoniin levels and CT38 seeks to reduce them. Finally the antidpressants are reuptake inhibitors while Cortene is attempting to target one receptor in the brain.

This article does propose developing CRF1 antagonists for use in depression but also suggests that they have a different mode of action

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1525061/

An alternative approach to antidepressant drug development targets the CRF receptor."
 

Cort

Phoenix Rising Founder
Could this have something to do with stmts Dr. Chia made to a patient in recent weeks about some important treatment breaththrough occurring soon. There was a post from a Chia patient last week or the week earlier.

I wonder if Dr. Kaufman and Dr. Chedda (sp?) know anything about this....and yes, what about Dr. Davis and OMF?

I hate when stuff like this is all cloaked in mystery. Why will it take Cort 3 blogs to release the full story?

We've already been waiting 25+ years isn't that enough time to build suspense.

Thanks for the initial info though, very much appreciated that there may be something to look forward to in terms of treatment. Especially a treatment that might actually fix us and not take a million years and treatments to do so.

@Ben H (any info from OMF avail?)

: )

Must be another breakthrough! We could use as many as possible. I was communicating with someone about Dr. Chia. For some reason I was really surprised at how inventive he was and how willing he was to try new things. I thought that was encouraging.

They are three LONG blogs! :)
 

Cort

Phoenix Rising Founder
Mifepristone! We're going to hear more about that....(not from Cortene)....Sorry to be a tease but I don't know if the information is out or if the researcher is ready to have it out but we're definitely going to hear about Mifepristone. I wrote a blog on it years ago because of its natural killer cell enhancing activities. I thought it was a really interesting drug.

https://www.healthrising.org/blog/2...al-killer-cell-drug-chronic-fatigue-syndrome/


I wonder what advantages this new CT38 peptide has over the abortion drug mifepristone (aka RU-486)?

Both CT38 and mifepristone act to temporarily inhibit the actions of the HPA-axis, and in both cases this is thought may lead to a HPA-axis reset. The idea is that the temporary inhibition of the HPA-axis resulting from taking these drugs for a few days or weeks facilities the axis reset.

From Cort's excellent article:


The HPA-axis reset achieved by mifepristone works in a similar way, and has been shown effective for major depression, 1 and psychotic major depression. 1

A mifepristone HPA-axis reset was also trialed for Gulf War illness, 1 but did not seem to help the symptoms, except some improvement in verbal learning (but did not improve other cognitive measures).



In terms of how the HPA-axis reset is actioned, the difference between CT38 and mifepristone is where they inhibit the HPA-axis. Here is the HPA-axis (and how it activates as part of the fight-or-flight response):

Stress ➤ Hypothalamus releases CRH ➤ Pituitary releases ACTH ➤ Adrenal glands release cortisol ➤ Activates glucocorticoid receptors

CT38 inhibits the effect of CRH (corticotropin-releasing hormone) by blocking the corticotropin-releasing hormone receptor 2 in the pituitary, and this then inhibits the whole HPA-axis.

Whereas mifepristone acts further downstream in the HPA-axis, by blocking the glucocorticoid receptor 2 (a cortisol receptor), preventing cortisol from activating the glucocorticoid receptor.

So this is how both drugs achieve an axis reset in their own ways; presumably CT38 must offer some additional advantages by inhibiting the HPA-axis further up, otherwise why would Cortene be trialing CT38 for ME/CFS.

Or maybe with CT38 they are not aiming to reset the HPA-axis, but rather reset some more local feedback loop just within the limbic system.



I am planning to try a HPA-axis reset using mifepristone in the very near future. I guess from its failure to make any major improvements in Gulf War illness, I should not expect it to help ME/CFS much. Although since the mifepristone HPA-axis reset did prove effective in treating depression, I am keeping my fingers crossed that a mifepristone reset may permanently improve the comorbid depression I often have, and lead to a better mood.

www.ec21.com is a good source of inexpensive mifepristone powder.
 

Cort

Phoenix Rising Founder
Does anyone know how long it takes for a drug to go through trials before hitting the market? I assume if this drug works for a cohort, the process may be hurried along since we have no approved treatments for our disease?
If it works well it should be speeded up. That said it will probably take far longer than any of us would want.
I wouldn’t say that at all. Don’t read too much into the delay, other than we all do the best we can with this illness.
I really apologize for not communicating during the delay. For some reason I didn't think of just posting something on Facebook and explain what was going on or coming on here (I just discovered this thread). I was just focused on completing the blog. Trying to get caught up...
 
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Cort

Phoenix Rising Founder
So I guess "CT38 might be curative" is no hype at all, then.

I think the blogs clearly state that the drug is highly experimental and that we don't know what will happen and I've made that point many, many times in the comments. In fact, I've made a point of it.

That doesn't preclude Cortene from possibly being curative if their hypothesis is correct. I don't see a disconnect between the two.

Cortene is not saying this drug will work. They're asserting it's worth a shot.
 
Messages
54
I think there are some big differences. Antidepressants can have a very wide mode of action while Cortene is much more targeted. Plus SSRI's attempt to boost serotoniin levels by blocking and CT38 seeks to reduce them. Finally the antidpressants are reuptake inhibitors while Cortene is attempting to target one receptor in the brain.

This article does propose developing CRF1 antagonists for use in depression but also suggests that they have a different mode of action

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1525061/

An alternative approach to antidepressant drug development targets the CRF receptor."

@Cort , would it be correct to say that another one of the big differences between SSRI's and CT38 is that SSRI's seek to ameliorate depression by moderately increasing serotonin via blocking its reuptake, whereas CT 38 - being an CRF2 agonist - seeks to spike serotinin much higher in an effort to trip the desensitized 5HT1A auto-receptors, which are responsible for causing the CRF2 receptors to internalize, thereby turning off ME/CFS. This would explain why lower doses of CT38 cause 'ME/CFS-like' symptoms, but higher doses would theoretically turn them off.
 
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Hopeful1976

Senior Member
Messages
345
I think maybe cautious hope is appropriate. I keep coming back to Ron Davis's comment about how complex the body is. It's dauntingly complex and plenty of time drugs that seem like they should work don't. I think it would take a bit of luck for a new drug based on a hypothesis to works AND it's certainly possible that it will,.

These guys do seem to be real sharp! If they think it has a good enough chance to spend a couple of years working on it full time, that's pretty good.

There's some animal data and some human data but it's limited; the drug is not being used in humans - so we don't have data there - and it's certainly never been applied to someone with ME/CFS. I think its experimental in the true sense of the word. Crossing fingers time :)
It's really very exciting - I can't help but think that something will show from this...
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
The heart rate situation is complicated - my understanding is that we have higher than normal heart rates during sleep and at rest and lower than normal heart rates during exercise (chronotropic incompetence).
The spread among individuals makes it hard to know. I have tracked my HR closely day and night so I know what is happening and I may be an outlier (very long term ME/CFS). My HR is low during the day and about 6 beats lower at night. During exercise? Well that is complicated by the POTS response.
I believe Cortene believes that higher cortisol earlier in the disease lead to lower cortisol later.
Of course we were never tracking our cortisol in the early stages--at least if we have been sick for decades.
 

Cort

Phoenix Rising Founder
The spread among individuals makes it hard to know. I have tracked my HR closely day and night so I know what is happening and I may be an outlier (very long term ME/CFS). My HR is low during the day and about 6 beats lower at night. During exercise? Well that is complicated by the POTS response.
Of course we were never tracking our cortisol in the early stages--at least if we have been sick for decades.

It should be lower at night -that's to be expected - but still higher than normal. It's the odd pattern of arousal when arousal shouldn't be there and depletion when the system should be aroused.

Acta Paediatr. 2011 Feb;100(2):289-92. doi: 10.1111/j.1651-2227.2010.02073.x. Epub 2010 Nov 17.
Elevated nocturnal blood pressure and heart rate in adolescent chronic fatigue syndrome.
Hurum H1, Sulheim D, Thaulow E, Wyller VB.
Author information

Abstract
AIM:
To compare ambulatory recordings of heart rate (HR) and blood pressure in adolescents with chronic fatigue syndrome (CFS) and healthy controls. We hypothesized both HR and blood pressure to be elevated among CFS patients.

METHODS:
Forty-four CFS patients aged 12-18 years were recruited from our paediatric outpatient clinic. The controls were 52 healthy adolescents having similar distribution of age and gender. 24-h ambulatory blood pressure and HR were recorded using a validated, portable oscillometric device.

RESULTS:
At night (sleep), HR, mean arterial blood pressure and diastolic blood pressure were significantly higher in CFS patients as compared with controls (p < 0.01). During daytime, HR was significantly higher among CFS patients (p < 0.05), whereas blood pressures were equal among the two groups.

CONCLUSIONS:
The findings support previous experimental evidence of sympathetic predominance of cardiovascular control in adolescent CFS patients. Also, the findings prompt increased focus on cardiovascular risk assessment and suggest a possible target for therapeutic intervention.

I actually found another study with lower heart rate during sleep (lol)