Discussion in 'Latest ME/CFS Research' started by Ema, Dec 22, 2017.
A long shot is better than no shot, but we still have to see if a clinical trial hits the mark.
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 down-regulating the corticotropin-releasing hormone receptor 2 in the pituitary (ref: 1), 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.
@Hip good luck. Be keen to see if it works
Damn. That sounds ballsy. What are the potential risks? (I'm in no way interested in trying it. Just curious why you're willing to do it.)
A rash can appear after longer term use, but for a HPA-axis reset, you only need to take mifepristone for a few days. Quite a few studies have tested mifepristone as a depression treatment, and I did not see mention of any significant risks.
This paper from Suzanne Vernon goes in quite some depth on how the HPA axis might be reset
It’s fascinating (albeit purely theoretical)
From the paper, her ideas on how this might be clinically
How did you hear about this HPA-axis reset? Can you post (either here or in your own thread) the research you found that led you to this?
Links to the research are in my above post. Further info in this thread.
I don't see that anyone has posted the link to Part II of this series on Cortene:
I can't cope with all these words.
When there's a cure someone give it to me please.
Cortene ll: A New Drug & A New Hypothesis for ME/CFS
I'm really excited by this! I wish I knew what Ron and others felt about it too....
I was asking myself the same question, but i don't think so:
As far as i know CT 38 / Cortene has not been approved for other disease.
Not quite the answer your looking for but see below an extract from the companies website. They describe this as "Early phase 2 proof-of-concept". I guess that if this is promising they'd need a larger Phase 2 and then Phase 3. I guess this is why the Cort Johnson article states "years".
Does anyone know if they can they demonstrate the presence/activation of "CRF2" receptor the drug targets?
If they can't identify those who respond i.e. by correlating response with the "CRF2" receptor then that seems like a potential problem i.e. assuming some of those with ME/CFS respond positively.
"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.
My, undeducated attempt to analyse this.
There are 2 5-ht2a receptor agonist that are effective in the at least the raphe nucleus, vortioxetine and flibanserin. At least in the short term, and only in the short term, you would expect them have some effect on CFS, but I could find no positive stories from them. Then they trigger autoreceptor desensitization. So, these drugs should cause CFS.
This is what I don't get. Wouldn't anti-depressant's be flipping out half the population (maybe they are but not to the extent most people with CFS have)? Also if people's auto-receptors can be permanently fucked up, seeming by innocous triggers or normal things like the flu, having sledgehammer SSRIs working on them would be a recipe for a ton of CFS. Like national crisis thing.
Side effects of SSRIs are like symptoms of CFS....that makes no sense to me.
I agree. SSRI's might well cause some CFS symptoms, but there is no evidence that they would trigger CFS itself. Considering that millions of people use SSRI's every day, I think it would be obvious by now if they played a role in causing or curing CFS, and neither seems to be happening. This is why I'm skeptical with these kinds of simplified theories, i.e. that screwing with one receptor would be curative.
I have taken them in the past (low dose)...their side effects were nothing like ME symptoms. Zero comparison.
I've been reading about seratonin and what it does in the body. As it is implicated in the whole body, it makes sense that an issue with it could cause the multitude of symptoms we all suffer from. I was particularly intrigued by the gut connection as I suffer terribly with stomach symptoms, as I know so many others do also.
You can also try a Google Site Search
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