In February of last year, Health Rising announced an unusual event was going to take place: a small drug company named Cortene was going to trial a new drug for chronic fatigue syndrome (ME/CFS). Cortene’s trial was unique in a number of ways. For one, it involved ME/CFS – a disease which rarely receives drug trials – and it employed a drug (CT38) not currently being used to treat disease.
Cortene’s drug trial was unusual in several ways – including the fact that it involved ME/CFS
Cortene proposed the novel idea that excessive levels of a receptor called CRF2 found on certain neurons in the brain were producing an unrelenting and hyperactive stress response in ME/CFS. Cortene believed that this improperly activated stress response was, in turn, responsible for the numerous downstream immune, metabolic and other issues that studies indicate are present in ME/CFS.
After an extensive review of the ME/CFS research literature, Cortene concluded that every feature of ME/CFS – from the gender differences to the triggering events – could conceivably be explained by CRF2 upregulation. It then began to privately raise money for a trial to test its drug in ME/CFS.
The goal of the trial was to normalize the stress response in ME/CFS by causing the CRF2 receptor to leave the surface of neurons in the brain. Because it’s impossible to measure CRF2 levels inside a live brain, Cortene assessed the drug’s effectiveness – and its effects on CRF2 activity – using improvements in symptom levels over four weeks.
The Study
The small first-in-patient trial took place at the Bateman Horne Center between July 2018 and April 2019 and was designed to help Cortene get answers to 3 critical questions:
- Is CT38 safe in ME/CFS patients? (It had been shown to be safe in animal studies and in a Phase 1 trial in healthy human subjects).
- Is CRF2 involved in the disease?
- Does a limited dose of CT38 bring about a lasting improvement in patients’ symptoms?
Results
The answer to these questions from this small (14 patients) non-placebo-controlled trial was a qualified yes. The drug appears to be safe. The ME/CFS patients, interestingly, reacted to the drug at far lower doses than the healthy controls did in a past study. That unusual sensitivity potentially validates Cortene’s disease hypothesis and could indicate that CT38 may be getting at a core part of ME/CFS. The fact that the limited doses of CT38 given to the patients appeared to produce long term (4 weeks) symptom improvement also supports this novel treatment approach for ME/CFS.
Next Steps
The results were positive enough for Cortene to move forward and start raising the money for a Phase II trial
Cortene’s next steps include filing its patent application, publishing the trial results and obtaining funding for a larger randomized, placebo-controlled Phase 2 trial which will provide much more information on the drug’s potential effects. That trial will attempt to confirm the initial trial results and determine the optimum dosing regimen; i.e. the optimum amount of drug to give patients and the optimum dose frequency.
Learn more about the Cortene Drug Trial for ME/CFS
- Cortene I: Cortene to Trial New Drug for Chronic Fatigue Syndrome (ME/CFS)
- Cortene II: A New Drug & A New Hypothesis For Chronic Fatigue Syndrome (ME/CFS)
- Cortene III – A New Drug for Chronic Fatigue Syndrome (ME/CFS): The Clinical Trial
- Cortene IV – The Cortene Chronic Fatigue Syndrome (ME/CFS) Drug Trial Begins
- Cortene’s website
Health Rising’s Mid-Year Recurring Donation Drive (Is Starting to Wind Up)
A little bit goes a long way with Health Rising! (Image from Nattanan on Pixabay)
Last year Health Rising brought you a startling development: a small company called Cortene was going to test its drug in ME/CFS. We’ve covered Cortene’s efforts thoroughly and will continue to do cover their efforts as well as others underway (the upcoming Naviaux Suramin trial and Dr. Klimas’s ME/CFS trial).
You can support us in doing that by chipping a little every month. Thanks to the 35 people who have done that so far (and the over 70 people who have supported HR with one-time donations) we’re about 75% of the way to meeting our goal of $500 in new recurring donations as our mid-year drive starts winding up.
Sign me up!!!
🙂
The next big (BIG) task is raising funding for a much bigger trial. Not an easy thing to do in this disease.
Oh so hope this proves positive and that at 70 ill be able to benefit soon along with many others
WoW can’t wait …
This is so exciting! Any idea how much patients improved? Where and when will the study be published?
We’ll find out when the paper is published. I want to point out though that this is a new drug, that is not being used or even attempted to being used in any other disease; i.e. it;s a new substance and the first trial was an exploratory one. Note that even though Cortene started off with what they thought was a very low dose they were immediately surprised by how sensitive the patients were to the drug, and had to get the trial reapproved to continue it.
Working out the best amount of dose to be given, the time period over which it should be given (it’s given in an infusion), the optimum infusion frequency and number -that’s all pretty complicated stuff. It will take a much larger study to determine how effective this drug is in ME/CFS.
Oh please get a move on ! So so fed up with getting older with this vile thing, I’ve had it for over 20 years and not enough money spent on research, no let up, just unremitting bloody symptoms and half a life
great news, but do we have any idea how long before this actually hits the market? does it have some sort of fast-track FDA status given potential need for this product??
My understanding is that FDA has actually been quite helpful. I believe that with the necessary funding and positive results it could be available in a relatively short period time. However, getting funding is not an easy task – particularly for a novel drug treating a controversial disease.
Hi Cort, I think the study is now up. I posted it on my facebook last night. Given the huge influx of long covid patients (you wrote this just before the pandemic!), I have a feeling this drug will be fast tracked. Looking forward to your next report! Thanks 🙂
they still need to fund a 2nd trial? Kind of surprising no one has snatched this up
Ultimately they need to fund a second Phase II trial and Phase III trials after that if the second trial is successful. That gap between the Phase II and Phase III trials has been called the Valley of Death for drugs because at that the money needs go way up.
The fact that ME/CFS is not a disease that big pharma is really looking to invest in presents a hurdle. If we could get a good diagnostic biomarker (nanoneedle?) that would surely help out.
Cortene, a very small company, has been quite creative so far – and are committed to moving forward…
Wow! This could be really good!
I would be interested in knowing who the patient group in the trial were? I don’t suppose they were severely ill patients? While an elevated stress response is a part of the disease I have a feeling that a lot of things are going on at the same time. It would be strange (but great of course) if one drug treated them all…
Cortene believes that the elevated stress response – centered in serotonin producing neurons in the brain – could be the core problem in ME/CFS. It could effect immune functioning, metabolism, etc. Time will hopefully tell if they are right. It would be nice indeed to identify the core issue in ME/CFS!
I have too long thought that the stress response is one of many issues but I’ve been wondering if it’s not more important than I have thought.
The patient pool was limited by the requirement that patients come from a similar elevation :). If phase II trials commence that will not limit patients in future trials.
When you say a stress response produced by serotonin producing neurons, do you mean the stress response is caused ny too much or too little serotonin in the brain? Like, is that why increasing serotonin, like with an SSRI, could help? Or is that a completely different thing.
As I understand it and this is a very complex area, Cortene believes that the hyperactive or as Cortene has put it – the prematurely triggered stress response in ME/CFS – is flooding the brain with serotonin.
Any idea why they wanted patients from the same elevation? Just having had a huge crash after going and spending 4 weeks at 7000 feet elevation makes me wonder.
It was the exercise testing.
Interesting. Does that mean that being on an SSRI would/could be….bad for ME/CFS patients? Like, could that actually make things worse? At least, theoretically.
This is a very complex subject. It has been addressed before but I’m not sure that SSRI’s necessarily apply to what Cortene is doing. I don’t remember the explanation though.
Me too Cort!!
I am convinced of it..
Actually started crying when I read this article.. thank you for sharing.. date we hope?
Cheaper solution than Cortene, and readily available, is quinine. https://www.nature.com/articles/srep03618#:~:text=Quinine%20inhibited%20serotonin%2Dinduced%20proliferation,production%20during%20incubation%20with%20quinine.
This sounds very promising!
Hi Cort,
I’m looking forward to the results. But I’ve noticed some people on Twitter totally dissing this drug. Do you understand their reasoning?
Thanks.
Andrea
No I don’t. I don’t know why anyone would bash a well-intentioned effort to help ME/CFS.
If they have questions or concerns it would help if they would put them on the blogs.
There are also people who bash recovery stories.
It’s an odd dynamic.
Cort, back when this was first introduced, it was to be a single dose. One time and Bam! cFS gone. Has that fallen by the wayside of reality?
Ask to the reaction to a tiny dose, that’s not really significant. Most CFS patients I know are hypersensitive to all drugs – alcohol, LDN, narcotics, etc etc. It’s part of the symptom package.
Still, this is good news. Thanks.
Yes, ME/CFS patients are hypersensitive to many drugs – not all drugs – but often many drugs) (LDN is not really a great example as it’s been shown to have very different effects at low and higher doses.)
As I understand it Cortene was able to show the drug caused distinct physiological effects at much lower doses than expected. They started off very low – and had to go much lower. (They had to go so low in fact that they had to notify the FDA of the changes and get new IRB approval for the trial – which caused the trial to take longer than expected.)
The effects that were caused were the same specific effects they anticipated the drug might produce at higher doses. It’s possible that that differs from the symptom exacerbation often reported by small amounts of drugs. In any case, it’s more fully fleshed out.
Jarred Younger, for instance, recently reported that he wasn’t able to determine that alcohol was producing any physiological alterations in I think it was FM patients, although alcohol intolerance was reportedly common.
This trial was not intended to test whether one dose or any number of doses would cause ME/CFS to disappear. It’s best to think of it as a small exploratory study that was designed to assess the effects of a limited dose of a new drug on ME/CFS. My understanding is that Cortene believes that permanent receptor internalization is possible and that the next study will look at dose ranges/frequencies that could produce that. We’ll learn much more about CT38’s effectiveness in that trial.
Even if it means that a dose is needed everyday forever ( or until something better comes along) , like insulin for type 1 diabetes, it would be good enough for me
could the side effects of too high a dose of the novel molecule mimic serotonin deficiency symptoms?
and theiretically, would giving tryptophan or ssri’s potentially relieve that?
The hypotheses is interesting however the article doesn’t mention which symptoms it helps.
If the hypothesis – which proposes that ME/CFS is caused by upregulation of this stress response receptor – it should theoretically help the core symptoms of ME/CFS; fatigue, PEM, cognition, etc.
Is there an anticipated date for publication of the study?
My understanding is that the paper is almost complete and will be submitted for publication in the not too distant future. However long it takes to get published, of course, is anyone’s guess.
Ok. Thanks. So similar to most other science things, it takes X amount of time. Can’t wait to learn more about the protocols and other important factors.
It’s encouraging that it made it through the recent trial, fingers crossed for more success down the track.
Thanks Cort. Yes, Bernadette asks the pertinent questions. Is there any way to learn what kind of patients these were? How severe? Ill how long? and what sort of result was obtained?
Cortene can’t report on the specific results until the study is published. I believe there was a pretty wide range of patients who were all diagnosed by Dr. Bateman. I imagine that means most of them were likely long duration patients. We’ll learn more when the trial was published.
I would doubt they were very severe or otherwise they could not tolerate the pre and post exercise test.
Most of us that are severe, very, very severe cannot tolerate it at all or basically even get to the test. That is one of the many issues with clinical trials with ME.
Hooray! Sign me up. 🙂
What specifically will the new drug address as far as symptoms go?
We don’t know what the drug will address as far as symptoms go – that will take more study – but Cortene has ambitious hopes for it. It believes that a hyperactive, prematurely induced stress response is a core part of this illness (which makes sense to me :)). If that’s caused by problems with this receptor – then if its drug works it should impact the core symptoms of ME/CFS – that means fatigue, post-exertional malaise, flu-like symptoms, etc.
As the blog noted there’s no way to know if Cortene is right about the receptor it believes is involved in ME/CFS as it’s impossible to assess the activity of this receptor in a live brain. Laboratory and animal studies, however, do indicate that this drug does effect that receptor and their research indicates that their hypothesis makes sense. What’s left is to fully test that hypothesis.
Time will tell.
Thanks for the report Cort…although some may not be keen on this proposed mechanism, for my own case it makes a lot of sense and I’m quite excited about this one…do we have an idea of when this trial will be published?
I think the paper is nearing completion. Then it will be a matter of getting it into a journal – and that can easily take months. Hopefully not but time will tell.
Cort do you know if there is any data on CYP interactions of CT38?
I’m afraid I don’t.
I hate to rain on anyone’s parade but this is quoted from Medicine.net .
“In the United States, it takes an average of 12 years for an experimental drug to travel from the laboratory to your medicine cabinet. That is, if it makes it.
Only 5 in 5,000 drugs that enter pre-clinical testing progress to human testing. One of these 5 drugs that are tested in people is approved. The chance for a new drug to actually make it to market is thus only 1 in 5,000. Not very good odds.”
I also find it difficult to buy the stress response trigger. According to a clinician who was involved from the very beginning of the modern ME/CFS epidemic, this started in San Francisco and LA in 1980, then appeared in Lake Tahoe in 1985 and gradually moved across the country. The clusters reported were from a group of teachers; children in Lyndonville, NY; a girls’ basketball team; a symphony orchestra, etc. Did these people all have stress at the same time? Finally, a study of 14 patients doesn’t say “anything” about safety.
All of us who have this terrible illness want to know “why” and can it be cured. I believe until we know why, there is no possibility of rational treatment.
Yes they did have a stress at the same time – they all appear to have been subjected to a severe infection. Stressors include infections. Before Cortene embarked on its multi-year effort to bring this drug to trial they assessed whether infections or other triggers could cause the receptor problem. They concluded it could. In fact, they believe the extensive theoretical testing they subjected their hypothesis to, is a real strength. They tortured it to determine if it could fit what they see in ME/CFS.
Time will tell but they believe that their hypothesis has the potential to more fully explain explain how and why ME/CFS got started than any other.
We’ll see! As Robert Phair – who’s metabolic hypothesis predicts something similar happening in the brain – has said, lots of beautiful ideas have been ruined by biology. 🙂
Although it seems like we should know what’s happening in order to treat something that’s not always true. Many drugs are effective without us know just how they’re doing what they are doing.
This is a sensible comment. The test stat is way off, not to mention that there is no proof, even a hint, that this receptor thing is relevant to nanoneedle diagnostic biomarker.
It really seems to me that with both these attempts we’re very much in an exploratory phase.
Cortene has a hypothesis that can only be tested using it’s drug.Limited testing has provided positive results. The nanoneedle is proving very, very (very :)) good at distinguishing ME/CFS patients from healthy controls but we still don’t know how it will fare with other diseases and what it’s measuring.
Cortene’s drug could flop in a bigger trial and the nanoneedle might get the same results in MS, fibromyalgia and diabetes. It seems unlikely but we don’t know.
The point is that I don’t think we should put too much pressure on either group to come up with THE answer. Any drug that moved the needle substantially on ME/CFS would be a huge help. I’m more in Dr. Klimas’s camp with treatments. While I would love for one drug to be “it” I think its probably going to take multiple treatments. The latest fecal transplant study, for instance, was really interesting!
We have some early encouraging results and all we can do is move forward and see what happens.
“Only 5 in 5,000 drugs that enter pre-clinical testing progress to human testing. One of these 5 drugs that are tested in people is approved. The chance for a new drug to actually make it to market is thus only 1 in 5,000.”
Well, there is already some very limited kind of human testing. So that should make odds higher then 1 in 5000. But 1 in 5 may be a tad optimistic.
I too remain undecided as I am helped a bit by my low dose SNRI (Cymbalta, good for me but for many a true disaster). But 15 mg a day is so low that it may not change serotonin levels that much and something else causes it to work.
The direction it is going is good so far. There are plenty of hurdles ahead but finding finances shouldn’t be the major one if preliminary results were good enough, that is if patients for example could financially participate by becoming shareholders if Cortene can’t find the financing model he prefers.
I wasn’t too optimistic a year ago and that did improve after reading this to being undecided. I hope he will prove my first guess wrong! And get the drug available at affordable rates :-).
I tried low-dose Cymbalta (20 mg) and had terrible nausea and GI upset. Is this common with ME/CFS patients?
I’ve never heard of the ME/CFS epidemic starting in 1980 in San Francisco and Los Angeles, prior to Lake Tahoe. Where can I find more information on this?
We may have the same clinician. I was told not to count on it in so many words but worse and detailed but I hope the clinician is wrong.
I find reports about interventions for CFS/FM questionable because chronic Lyme disease and chronic fatigue syndrome are, too often, indistinguishable, and the researchers involved do not even screen patients for Lyme or other tick-borne disease. It is intellectually dishonest work, in my opinion.
Thanks Dr. Shepler. Talk about another knotty and too often muddy area of ME/CFS that needs more clarity.
Thank you, Cort. Also for your responses to some of the questions/comments. Again a new thing thrown into the mix. Even so, I appreciate seeing something hopeful and positive today (that doesn’t involve brain stem surgery!) …even if it’s “untidy” as some of the comments have indicated. I don’t mind atm. Some days (like today) I just need to see that there might be another possibility to give me (us) some hope.
Yes – something that doesn’t involve brain stem surgery would be preferable! 🙂
What is the nature of the new drug? Note that crf2 is a corticotropin releasing hormone receptor. Do a google search and you will find there are two types of corticotropin release hormone receptors — i.e., crf1 and crf2. Likely the ;new drug has something to do with either blocking the transcription of crf2 so that there are a reduced number of receptors for CRH from the hypothalamus, or it may be a molecule that sits on the crf2 receptor and blocks it to diminish its activity. Just a guess. Here’s an article that implicates crf2 in arthritis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2557030/
I am a cynic. Drug companies placate people with inferior products that have risks and side-effects failing to look for the ultimate cause or cure of an illness. Sick people are profit centers.
I also distrust the researchers working in CFS/ME/FM because, to my knowledge, none of them are knowledgeable about chronic Lyme disease. I strongly suspect that one of the reasons CFS and related conditions has been ignored is BECAUSE of its resemblance to chronic Lyme disease, which powerful interests inside the CDC and the Infectious Disease Society of America (“IDSA”) want to hide.
It perfectly suits their interest to call cases of chronic Lyme disease “something else” in order to make it simple to carry out their experimental human Lyme disease vaccine studies that would otherwise not be approved by institutional Review Boards that exist to protect human research subjects.
The scientific fraud is too dense for the average person or even most clinicians or researchers to comprehend. But it is hiding in plain sight.
I am disgusted by how the CFS et al community is manipulated and deprived of answers.
One of the big “tells” diagnostically is who experiences what are called Jarisch-Herxheimer reactions with antibiotic administration? Jarisch-Herxheimer reactions only occur in the context of three infections: syphilis (Treponema palladium), leptospirosis, and species of Borrelia (Lyme disease). Then, you want to look for the release of pro-inflammatory cytokines using laboratory testing that occurs coincident with antibiotic administration. If a person experiences a clinical Jarisch-Herxheimer reaction or has laboratory evidence of such, one would look for BACTERIAL INFECTIONS. And if you don’t have syphilis or leptospirosis, what’s left except Borreliosis (Lyme disease)?
Note that females produce less antibody to Borrelia than males, with the sex difference being extreme enough to cause females to have statistically significant negative laboratory tests for Borrelia (Lyme disease) compared to males. But the CDC and IDSA do not want you to know that.
Presently, I knew of few physicians who know how to work up a case of chronic Lyme disease. So what most patients get who present with symptoms may simply be a diagnosis in the spectrum of CFS et al that has no interventions, and the pathogenesis is not even understood. This is bullish**.
The scientific dishonesty and incompetence leaves me with never ending heart burn. Anyone told they have a CFS spectrum disorder should first be given an antibiotic challenge test, and multiple tests for stealth pathogens associated with tick and animal transmission. This is not occurring.
I believe that the CDC and the IDSA perpetrate scientific fraud. They are not interested in patients, they are invested in their relationships with Pharma and function as a front for private or pharmaceutical interests related to stealth pathogens. It is a travesty.
Dr. Shepler holds an interest in the neuropsychiatric manifestations of infectious. Skills and Expertise
Psychopathology among others
I would so love to speak with you!! I had a very delayed standard Lyme test and it was negative. Finally got a bunch of lab work that included the b word type of tick dx and out of 20 tests it was the only one they forgot to run. I thought that is strange. Anyway, I had every symptom and had many ticks small and large due to living on a farm and being outdoors a lot, after the Meg test and continued severe symptoms that were getting worse and becoming more in the neuro damage category, pain, neuropathy, brain fog, unable to multi task, felt toxic all the time, you name it, I finally begged and cried for tick treatment with antibiotic and I had a herx reaction. I didn’t really know much about it at all at the time or even what a herx reaction was but he told me to stop the drug and that it wouldn’t work. Still only the standard tick test was done. I have been sick now since 2010, I am an RN and was a VP for a top 3 hospice company in the US. I worked from home for a while etc but finally the symptoms were too bad and I was no longer able to work or think at the end of 2013. Sad sad . I believe in ME/CFS but I believe with all my heart that a tick caused the end result of ME. I wish we could chat about your thoughts!!! I hope you are on Facebook or somewhere haha
My Initial on Facebook are SWC. I will look you up today.
Not that a diagnosis of chronic Lyme disease is not any better than a diagnosis of CFS with respect to the suffering individual. The CDC/IDSA has made sure that no progress is being made exploring potential treatments for chronic Lyme disease. In fact, they try to claim it doesn’t even exist. The new draft guidelines for Lyme disease from the IDSA continue to falsely maintain that 20 days of doxycycline produces a bacteriologic cure (i.e., eliminates ALL bacteria from every nook and cranny of the human body).
There are a plethora of scientific studies that contradict their ideologically-based contention, but that they ignore.
So, would you rather have chronic Lyme disease or CFS? It’s a coin toss.
And what is the significance of the recent published work by Kris Newby drawing the connection all the more convincingly between the dissemination of Borrelia and a U.S. biowarfare laboratory leak? Is this why the CDC/IDSA will stop at nothing to get a purported “vaccine” on the market? That they truly know the destruction caused by this disease, the huge potential for backlash if the connection is ever securely established? That’s all for speculation. But one does wonder why there is such extreme preoccupation with vaccine development, and experimenting on the human population with various bioengineered Borrelia vaccines—-for a disease easily cured by 20 days of doxycycline.
And we know the extreme limitations of the bioengineered Lyme vaccine they are now planning to push on the public in both North America and Europe. You can only engineer so many proteins into a vaccine. And there are many strains and species of Borrelia. So to market this vaccine as a Lyme vaccine, they lie and say there is not Borrelia of important to human health in the U.S. South and West. Why? Because the proteins on the coats of these forms of Borrelia don’t match the ones they are trying to sell in the new vaccine, and you can’t pack all these proteins in one vaccine.
Lies, lies, lies, lies.
It is unfortunate that the chronic Lyme disease community and the CFS community have achieved separate identities and separate goals. Yes, certainly there may be other etiologies driving pathology in the CFS spectrum of disease. But the CFS community is not even getting the basic “rule out” testing they need and deserve. And we know that power likes to inculcate divisiveness to maintain its power. To that degree, they have succeeded in dividing the two communities.
Now there are claims that biotech companies are going to develop products for chronic Lyme disease. This is utter nonsense, and we will only get the type of inferior, useless products manufactured for CFS spectrum patients. Drugs that are palliative, and may have many serious side-effects and risks that go unacknowledged. But they will be pushed on the Lyme community, and you can predict there will be people who will, unfortunately, embrace them.
In Lyme disease, the problem is chronic infection. But those in power (CDC/IDSA) will try to engineer around that leaving people sick and without answers. Telling them they have “something else” and “here’s the drug for it.”
The scientific literature is being filled with falsifications that will affect the science of these diseases for decades.
A drug like what is being proposed by Cortene could modulate the down stream affects of chronic infection. Chronic infection is a stress on the human body.
This is a problem that is being unaddressed, for example, with the development of “biologics” for rheumatologist disease. It has always been postulated that the inflammation associated with rheumatologist diseases is caused by infection. The “biologics” developed to treat rheumatic disease DECREASE INFLAMMATION, and inflammation is what keeps chronic infection in check.
Thus, there are BLACK BOX WARNINGS on the package inserts of these pharmaceuticals stating that INFECTION may appear with their use. And it does.
It appears to me that what is being studied in many areas of disease are the DOWNSTREAM EFFECTS of CHRONIC INFECTION. As a result, what we get are palliative pharmaceuticals, if they work at all
Opinionated? Just a little. And I have paid a big price for expressing these opinions, and continue to do so. But if my opinions aren’t on target, why would anyone among the powers that be even care about who I am, or take the time to complicate my life? I would simply be a loose cannon of no relevance to be ignored. But, no, they don’t ignore me—in fact, they have worked to destroy me in various ways.
Please bare in mind that we have little incidence of chronic Lyme in NZ. There are some cases where people have immigrated into NZ from the US and Australia. (Even the Australian cases are suspected to be Ross River Fever) However it almost absent from the Maori population. I know you may argue that all people have not been tested “properly” for chronic lyme but it just does not stack up. Many of the people I have dealt with who have ME/CFS contracted the illness after glandular fever, confirmed HHV4. Not all but most of the people under the age of 30 have been HHV4 infections.
There is an overlap between lyme symptoms and ME/CFS symptoms but there are many overlaps with chronic immune dysfunction following infections.
There is an awful lot more to Lyme disease & that is the Alpha-Gal Meat Allergy from a tick carrying & passing on the mammal protein, it is a wonder why Antibiotics are
useless…Everyone with Lyme ME/CFS needs to be tested for Alpha-Gal, beef, lamb, pork & the ranges first used 30 to 100 are wrong, anything now above 0.02 is a
positive alpha-gal test…It also would explain all reactions to numerous medicines, foods, vitamins minerals that have alpha-gal, magnesium stearate & also any
carrageenan…Alpha-Gal SAAT Remission on Facebook is a good Group
What ever became of Ampligen?
There is some good news about Ampligen. Dr. Peterson, the Simmaron Research Foundation, Dr. Maureen Hanson and the CDC are assessing Ampligen’s effects on Dr. Peterson’s patients to see if they can figure exactly what Ampligen is doing. Hopefully that information will help Hemispherx – the producer of the drug – move forward.
FYI – Hemispherx Biopharma has changed names to AIM ImmunoTech Inc. This article says the name change is effective on September 3, 2019, https://finance.yahoo.com/news/hemispherx-biopharma-inc-changes-name-105000500.html
It’s rubbish
Cortene may help..since it might help relax the stress response which could get us out of the dauer state that Robert Naviaux talks about in his research. Its just a thought of mine since I know that stress makes CFS/ME much worse.
I have to say I find the potential interconnections between Cortene, the Dauer response, Dr. Klimas’s model of a stuck, suboptimal state, a chronic “sickness behavior state”, the Japanese idea of turned off motor activation pathways, the freeze response, and others that I can’t think of – really interesting 🙂
I start thinking like this: People alive right now have been exposed to more novel environmental and physical insults than probably any generation that has ever lived before us – despite the improvements in quality of life. The variety of man-made air and soil poisons alone is disgusting, which is essentially war on the microbial populations that have sustained us throughout history. Our diet is unique, and everything that is bad for us has been subsidized. We eat crap food from crap soil. So my point is this: some genetic subtypes get varieties of diabetes, other genetic subtypes it’s cancer, and yet another, gets autism, another gets the hyper-stress response CFS. Our deer have chronic wasting disease. The bats have a deadly nose fungus. The bee hives collapse and die. The ticks are so sick and carry loads of bacteria. Every time I whine about the CFS, I remind myself that I don’t have cancer or diabetes. Not yet anyway. I
I am intrigued by this and the drug to treat a dysfunctional crf2. Lyn Shepler is correct the drug is either an antagonist of the receptor or is blocking transcription. I’d pick the former – easier to do and test. There have been quite a lot of crf1 and crf2 antagonists tested. Such a drug will need a lot testing as side effects may be a problem with those people who have significant MCS with their ME/CFS.
I suspect that the excessive crf2 outflow is a downstream effect but still one that could be successfully corrected. I do think that the wide variety of symptoms is more related to a channelopathy, probably an autoimmune dysfunction. This better fits the findings of the Griffith University Neuro-immune disease research centers findings of TRPM3 dysfunction on NatKcells. We will see!
If this drug is successful and eventually makes it to market will it be available in just the US or other countries? Is there usually a long time gap between approval in other countries (I’m in Australia)
If it’s successful in the US, I’m sure there’ll be a big advocacy push from patient organisations like Emerge and MEANA (ME Advocacy Network Australia) et al to get it into Australia, as well as other countries. Having had positive noises coming from three main political parties during the last Fed Election, re ME/CFS, hopefully they’ll see the economic sense of getting all c 125-250,000 of us well again and off benefits!
Of course it will be easier if it were to be a one-off dose as first posited, which presumably would less expensive than something you have to stay on for life.
This may explain why I instinctually Knee I shouldn’t take an SSRI but after my dr pressured me to try, within 7 days I developed very scary seretonin syndrome!!!! From this hypothesis, i had way too much seretonin to start with and I went over the edge on ssri’s
My worry is that -as Your excellent blog has shown, Cort, different keys work on different patientpopulations in the me/cfs-group. Some benefit from antivirals, some IVIG, some surgery, some mestinon or mariuana, some Ampligen or cyclofosfamid etc.
What if Cortene’s hypothesis is right for a subgroup, but because of heterogenity regarding fenotypical variants, the drug will not work on everyone -and therefor not be approved?
Ps thanks for Your Excellent Work ??
Great question. I believe that’s a big issue for any drug in ME//CFS. How do you get beyond the heterogeneity present in the disease? I don’t know. The Simmaron Research Foundation is leading a study which is attempting to do that with Ampligen.
If the drug worked great in a meaningful sub-population then it would easily be noticed by anyone knowing basic statistics.
For most it would then do nothing or work negatively due to side effects. Another smaller group would be on a totally different corner of the graph.
Then it would be no different then many other drugs: works for example well in about 1 in 5 patients but not in others. Doctors knowing the patient has this disease then subscribe it for a week or so and ask to come back next week.
Monica, I also got a serotonin syndrome after using a low dose of trazodone for sleep/insomnia for a short while. I also got very ill every time I tried 5HTP. I can’t take any meds that increase serotonin.
I am the same, including that I can’t take omega-3 fatty acids. Three days of a medium dose of extremely high quality fish oil and I experienced distorted reality, which resolved after stopping the fish oil. This happened again after days of eating quite a bit of grass fed butter (high in omega-3s).
I have a history of problems with even very small doses of SSRIs (even prior to ME/CFS). Testing for liver enzymes showed that I’m a slow metabolizer for SSRIs
I’m convinced that, at least for me, serotonin is a key issue.
Is it known whether the drug would help people with cfs whose main symptoms are multiple chemical sensitivity.
There’s now way to tell. This was a very small study. Cortene does believe it’s hypothesis could explain things like light/chemical, etc. sensitivities.. lot more work needs to be done before we know about its effects with things like that. I would give the Dynamic Neural Retraining System a try to be honest. Some amazing stories coming out of there. I know of two people who tried DNRS after reading about Cortene’s hypothesis and were successful.
Cort, forgive me, this might be too personal, but have you tried the Dynamic Neural Retraining System?
Do you know if the drug called ‘Antalarmin’ which I think is on the market in some countries in Europe has a similar effect to the drug tested by Cortene ?
Cort, you said that the original CFS outbreaks were caused by an infection. What infection? Do you know? Answering this question will present the most appropriate solutions.
This is critical because certain medication exposures can cause serious reactions in ME/CFS patients.
In my own experience, a trial of medications for Mast Cell Disorder triggered Narrow Angle Glaucoma which led to laser surgery and then a very serious condition called carotid cavernous fistula. This involves the rupture of the carotid artery behind the eye that then attaches to the vein behind the eye. You can lose your vision or have a stroke. A four hour brain operation by an
top specialist repaired the problem. I now have platinum coils in my brain. I will need to use special drops in my left eye for the rest of my life to hopefully preserve my vision.
A trial of Valtrex at 3000 mg. a day for three months led to joint pain, dizziness and several falls that resulted in a broken finger and two broken toes.
A recent trial with nimopidine caused severe stomach pain and loose bowels even weeks after I stopped taking the drug.
Re. antibiotic reactions in Lyme Disease: In a personal correspondence from the HHV-6 Foundation, I was told that certain antibiotics cause HHV-6 to activate more.
This is why my main concern about this new drug is the very small number of patients tested for the safety profile.
I just heard from my sis and she was asked to be in the trial for this drug. She is in Utah. She declined, afraid to take chance.
But is going to be in another genetic study. So we will see…….
I have a 28 year old daughter who has been declining over the past 5 years. She is now bedridden. Can you PLEASE tell me who is the contact for this study/trial. I will do anything (including having her in this trial) to help her. Its heart breaking down to the cellular level to see her losing her life little by little.
Thank you …Please help with information.
They already have the trial underway. They are only using Dr. Batemans patients, as far as we know. Also those who live in Salt Lake as to be on equal field as to altitude. She would have to be an established patient there. Not sure the wait to get in.
My sis and I were in the Mitrochondrial Genetic study with Dr. Alan and Kathleen Light. They too are at University of Utah.
I’m signed up to be in studies with Dr. Jerod Younger at University of Alabama now. Was asked to be in one drug trial, but another medicine I’m on prevented my participation in that one. But I knew the drug and tried it on my own. Did not work for me. Can’t talk about it though.
I’m now signed up for a genetic screening/test at University of Alabama and just got my appt. scheduled.
There is research going on. You have to go on line and start calling and keep calling to get into something.
As for genetics and subset types, they have all that information in Utah. Since the patients are probably Dr. Batemans patients and live in Utah. Both my sister and my blood is in the blood bank approved for further research. Our mitrochondria presented much differently, despite us being sisters and both having CFS and FMS. So, they may be using certain people based on that. Me just guessing…….they didn’t call me.
My experiments of recent have me upping dopamine and oxytocin and I’m seeing improvement. Also some herbs that help blood flow and oxygen delivery and reperfusion. Still new in my trial. We will see………..
might be because of herbs or meds that a personhas tried that could affect same systems that influences choice of patient?
would dopamine be one of these?
Yes, that’s what got me in this Alabama trial. One of my medicine would interact with the drug they wanted to trial with.
If you think about this hypothesis, if serotonin is too high……might another neurotransmitter be too low? Or some other level is out of balance. The goal being homeostasis. I also tweak things in regard to glutamate. Also with my having mast cell issues, some of my mast cell stablizer and POTS medicine affect calcium channels.
I do trials in areas that seems rational and seem to fit my symptoms. So far, things are definitely improving.
Thank you for your information, and help. I reached out to Ron Davis, and I suspect that he is inundated, and doesn’t take contact from the public. He also has his own family challenges. I appreciate your input.
I hope all continues on an upswing for you and your family. God Speed to the Cortene trial.
I believe in my illness, stress is an enormous factor. Massive stress was present and then flu when this all began 12 years ago. Then when my stress levels rose, I became sicker.
More recently I became aware of just how out of control my stress levels had become. I had actually just got used to being permanently wired, not sleeping etc
When I actively brought my stress levels down, I began to get a bit better.
One of the most stressful parts of this illness for me, is not being believed, acknowledged and validated. Over the years I’ve generally had the dismissive attitude of the medical profession. My family haven’t believed me, though some are coming round to the idea.
My point is this: as social animals, to be ostracised by the group means danger. Animals separated from their herd are easier targets for predators. Isolation can mean death.
So, for years I have lived as a sort of exile, with extraordinary symptoms any ‘normal’ person would probably be placed in an intensive care unit.
The more problems I spoke about, the more people thought I was just talking hysterical nonsense (as Dr Charles Shepherd says he was taught in medical school).
I feel out of step with the whole of society apart from on this website and in other ME/CFS arenas. I believe this is a source of stress that is not fully recognised.
The money governments have spent to help research such large me/cfs populations is a mystery. Imagine if a treatment could be found to improve symptoms by 20 percent. That could be enough to get a lot of people back to work. I have heard an estimate of about 50 percent of patient cfs cannot work. Hundreds of thousands or maybe more could get back to work. It seems to me that the impact on the economy of so many unemployed should count for something by governments designing funding programs for cfs.
Also my stress levels go up if I don’t sleep ‘well’ and if I eat food that I’m intolerant to. I then feel more tired and I’m drawn to those foods that give me fast energy but they’re the ones I have a problem with, like sugar/fructose/wheat/dairy and so I would just be caught in an endless vicious circle.
I have broken this now by reducing my stress levels, getting better quality/deep sleep and absolutely avoiding all the food that I’m intolerant too.
I’m not completely normal but I can function, work part time and as a consequence engage a little more in ‘life’.
I feel however, like I’ve been through something hugely traumatic and am sort of reeling from the past 12 years and especially the last 3, when I became so ill.
I think I would become so much better if I could have a very long and relaxing convalescence somewhere stunningly beautiful, like the Swiss Alps…
Dream on!
Thank you Cort for another excellent article! I love what Cortene is doing and admire their creativity and daring. I was wondering how their theory could be linked to three major areas that are definitely playing a role in my illness: early life stress, gut permeability and mast cell activation. I found these interesting articles:
1. Deciphering the Interaction of the Corticotropin-ReleasingFactor and Serotonin Brain Systems in Anxiety-RelatedDisorders
https://www.jneurosci.org/content/jneuro/29/44/13743.full.pdf
This article proposes that small amounts of CRF activate CFR1 receptors and that large amounts of CRF activate CFR2 receptors. CFR1 seems to be linked to the fight response, CRF2 to flight or freeze. It seems that this serotonergic signalling becomes much more sensitive in people who have been exposed to early life stress.
2. Role of Corticotropin-releasing Factor in Gastrointestinal Permeability
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288093/
This article suggests that both CRF1 and CRF2 activation leads to increased permeability.
3. Corticotropin releasing factor receptor 2 exerts global suppression of mast cell degranulation and associated pathophysiology.
https://www.jimmunol.org/content/198/1_Supplement/222.27?utm_source=TrendMD&utm_medium=cpc&utm_campaign=J_Immunol_TrendMD_0
This article links the CRF1 receptor to mast cell degranulation and the CRF2 receptor to mast cell inhibition (!!)
I don’t have any medical background whatsoever but I believe that Cortene is on the right track. But perhaps the problem is high levels of CRF. I worry that targetting only one receptor is not enough to restore the balance. I strongly believe that I have MCAS (however I can’t get diagnosed in Belgium because the illness isn’t recognised here). So, inhibiting the CRF2 receptor might be detrimental for me because, as I understand it, that would increase mast cell degranulation and histamine.
I agree. CRF1 plays also a major role in ME especially if you have panic attacks and anxiety feelings without a mentally cause.
When i wrote 15 years ago that ME could be caused by an abnormal stressresponse (activates the ANS and was a physical problem not mentally. I got the whole ME community over me with angry reactions. What has been changed that ME patiënts now embrace this theory? By the way is it only a subgroup! You know if you belong to this subgroup if you feel rushed and hyper. If you feel relax and calm you don’t belong to this ME subgroup. ME is a an abnormal stressresponse to any stimuli. But why? It still clould be for compensation to survive.
Yes, it seems that CRF is active in the sympathetic part of the nervous system which is permanently activated. CRF decreases stomach acid, affects autonomic functioning, basically gets the body ready either to fight (via CRF1) or flee/freeze (via CRF2). I do feel rushed and somewhat anxious all the time! I wonder if Cortene is still looking too much downstream, as I believe many researchers are still doing at this time.
I agree with you Gijs and Conny. I would be in the hypervigilant subgroup.
I say I would have been stressed before I was born, stressed throughout my childhood, maybe a bit ADHDish (I am 58 – who is honestly going to care now!)
But that was ‘normal’ for me. I remember saying to a friend when in my 30’s, I think I find life more difficult than other people.
I have to really focus on relaxing. I’m better off doing things – I’m not great when life is unstructured – I’ll sort of flit from one thing to another.
So, that becomes a problem with a condition like this, where energy is in limited supply. They say appliances in the home that are on 24/7, like fridges and freezers use a great deal of our energy usage.
Despite looking like I’m fairly relaxed, underneath I’m not.
I found watching people like Daniel Siegel very interesting, as he does some fascinating and entertaining videos on the whole fight, flight, freeze response.
I think the problem with the whole CBT issue, is that any mention of stress is going to bring up thoughts of ‘it’s all in your head’.
I trained as a counsellor/psychotherapist and in my own experience, this condition goes way beyond the regular stress/anxiety response.
In me, it seems to tap into the powerful autonomic nervous system and immune system, which I don’t have conscious control of.
However, I have tried to figure out what is setting them off and systematically work my way round and round trying to calm everything down. I have tried to deal with any issues that I felt overly burdened by, have ruthlessly fine tuned my diet and I do take supplements as I believe I have been unwell for 12 years and am probably deficient. I have also managed to break the endless cycle of shallow sleeping, feeling exhausted, eating the wrong things that set me off and going around again.
But I have to do all the changes, all the time. So I suppose I’m managing my condition rather than being fixed. However, I think that if I can stabilise myself, then maybe it’ll become the new ‘norm.’
The brain is the most energy intensive organ in the body. Think how much energy it uses up if it can’t relax, if as Cortene believes – it’s been put into near constant action by a prematurely activated stress response?
” this condition goes way beyond the regular stress/anxiety response.”
I think it’s very different from anxiety – I just do not fit the anxiety profile; something different is going on.
It’s a great question. I remember the days when mentioning “stress” could leave you apt to being tied up by the yardarms. One thing, I think, is that we can now differentiate between “stress” and the stress response – which involves the HPA axis and autonomic nervous system. We now know that both these systems are disrupted in ME/CFS, that both effect the immune system, that the ANS is involved in many things from blood flows to muscle activation. We also KNOW – studies have shown – that depression is not a core feature of this disease.
In short I think we’ve differentiated between the behavioral aspects of “stress” and the physiological problems associated with a malfunctioning “stress response”.
Je pense que la dépression n’est pas une caractéristique de ME mais un effet secondaire. Il me semble aussi que le stress est lié à la perspective de devoir faire des choses qui dépassent notre niveau d’énergie. Pour moi, il faut économiser son énergie et refuser la pression de l’entourage. Merci Cort pour tout ce travail intelligent et rigoureux. Ce n’est qu’en persévérant qu’on trouvera.
Does anyone know the dose of CT38 that was used in the studies?I can’t wait for the drug to be fully tested before it becomes available.
I remember from looking into this earlier that CT38 is a blend of branch-chain amino acids (BCAAs) but I don’t know the dose.
The dose was a real issue! It impacted patients at a much smaller dose than expected. I think that’s good news as if CT38 works out, it means less expense for the patients! Now come questions of what the optimum dose is, how it should be delivered – via infusion or via the skin, how quickly it should be delivered and how often.
Cortene’s goal is to make the CRF2 receptors disappear from the surface of specific neurons in the brain. Given the results we can assume that happened at least to some extent: the next challenge will be to optimize the dose and see what happens.
As a specialist teacher of dyslexic/ADD/ADHD and ASD students, as well as mother to a 22 year old with ME/CFS, lyme and co and mould illness, I would like to make two points.
Firstly, there is a huge crossover between ME/CFS and picture thinkers such as those I teach. These are the deep thinkers, the chronically stressed who can’t work out why (despite often having great intelligence) they often struggle with reading, comprehension of the written word and socialising (or at least they struggle because of the way these things are taught in most education systems around the world). In my opinion, that is enough in its own right to set off a chronic stress response, apart from any physiological differences in the body of the sufferer, so the “stuck in fight/flight mode” that this drug company are proposing makes perfect sense to me.
Secondly, having researched ME/CFS extensively for the past 10 years in order to try to get my son well, we have got him from bedbound to 95% normal energy with initially a few antibiotics and other drugs (later gave most of those up) and mainly extensive herbal supplementation. But the one thing that keeps rearing its ugly head is that “wired”/stressed feeling. We are now trying Annie Hopper’s DNRS system(initial results are very hopeful) and it certainly does seem to have a very similar basis to the theories Cortene put forward. Testimonials for DNRS and other similar therapies do appear to be “near miraculous” but if this is the mechanism or one of the mechanisms at play in chronic illness maybe it does deserve a closer look. Perhaps oncethe malfunctioning fight/flight system is calmed, the immune system can start to do a better job at keeping infection at bay.
Congratulations on getting your son so much better! And good luck with getting that “wired and tired” (whoever came up with that phrase really hit it on the head) and weird stress response down. Does he still have mostly normal energy?
“we have got him from bedbound to 95% normal energy”
Congratulations both of you for achieving such fantastic and rare result. Would you have written upon it in the recovery stories section? If so, where? If not, many would like to hear more of what you’ve got to tell.
I am nowhere as far as your son got. I’m now at about 25% of my normal abilities. I can mainly get my brain working well for a limited amount of time spread over the day. But that still depends upon my ability to “push through” and my ability to “push through” depends on how well I can “surf” upon my stress hormones.
Maybe that is what “But the one thing that keeps rearing its ugly head is that “wired”/stressed feeling.” says: Your son might be able to get to 95% of functionality under the condition that he pushes through a lot more then a healthy person (and is aided in that department by stress hormones like cortisol, noradrenaline and adrenaline boosting energy levels)? As an ME patient he must have plenty of experience pushing through. If so, he might have still far less a buffer then a healthy person.
I’d be interested to hear your ideas upon this one.
kind regards
Yes Anne, I agree with everything you write.
Annie Hopper’s DNRS idea seems very interesting and probably along the same lines as Dan Neuffer’s ANS Rewire program.
It was reading Dan’s book CFS Unravelled and watching his videos and recovery videos that enabled me to regain my health.
I believe our brains/minds are extremely complex and infinitely powerful. We are only alive on this planet now because our ancestors survived, whilst others perished. Their fight, flight or freeze response would have been crucial over the thousands of years of evolution in their survival.
Daniel Siegel has a very funny part of one video where he’s explaining how our sympathetic nervous response is instantaneous and that we have no control over it.
He mimics his nervous system saying something like ‘Listen, Danny Boy don’t think you have any control over me, I’ve been protecting you for years…’
A while ago I was standing at my 15 year old son’s door regailing him with the ‘it’s all in your head’ stuff, with great indignation. From his chair in front of his computer, headset on, friends waiting for him to rejoin the game he said ‘Well it is in your head’.
I looked at him steadily, took a deep breath, had to agree with him and had to walk away!?
However, there is a monumental difference between the assumption that ME/CFS is an imaginary illness and that a person just needs to realise that, and truly believe that they’re well, to get better and an acceptance that one of the most elusive and complicated organs of the body is involved (the brain) combined with other vast systems like the autonomic nervous system and the immune system.
I think the current culture within the medical profession helps neither patient nor doctor.
The doctor’s were once at school are were amongst the young people who achieved the highest grades. Through a lot of hard work they got to medical school, survived and qualified as a doctor.
They then get to spend a great deal of their life with patients with all sorts of problems, possibly chaotic lives, unhealthy lifestyles and with no intention of eating healthily, stopping smoking etc
Doctor’s have a certain degree of knowledge and a lot of power. Patients are disempowered.
When I was ill in the beginning 12 years ago, I went to the doctor for help as I didn’t know what was happening and I wanted to get better.
Many years followed of different doctors referring me to different consultants. As each one couldn’t find anything wrong, they assumed there wasn’t anything wrong with me.
This was so demoralising for me and at times I believed them. The problem was everyone else like family and friends believed there wasn’t anything ‘really’ wrong with me either.
I think I snapped out of that thinking when symptoms started to escalate and I was terrified. Stress levels rocketed.
I just began to see all sorts of gaps between my experience and the medical professions view. As one GP and a Consultant Immunologist said to me ‘The medical profession doesn’t do food intolerances.’
I just thought how stupid.
So, I’ve just empowered myself, spent years researching with a suboptimal brain!
However, even with a brain that at times couldn’t remember, couldn’t hold or sort information very well, was often in a shallow unrefreshing sleep, at least it was a brain that was searching without prejudice and pre-judgement.
I think it helped that I’m a fairly independent thinker, which has landed me in a lot of trouble over the years, when I have challenged practices I thought were inappropriate in all sorts of circumstances…
Compliance is maybe more comforting; the belief that a benign power is in charge and will make everything ok.
Realising that benign power may either consciously or unconsciously have its own interests and beliefs at the forefront of its decision making is unsettling at the very least.
I believe we are on the frontier of a new, novel way of thinking. I think the relationship between the ‘patient’ and ‘doctor’ as in the relationship between ‘therapist’ and ‘client’ is paramount in the level of effectiveness of the assistance offered.
If this power dynamic becomes unhealthy, disrespectful, oppressive and so on then immense damage may be inflicted on the person with the least power, usually the patient/client.
I need to go!
I have lost two great long pieces I’ve written due to a misunderstanding between myself and my aging phone. My computer has packed up and is in the menders.
‘I think it’s very different from anxiety’
I agree but I believe anxiety makes the situation worse as it can increase inflammation. I developed asthma in the last 12 years and stress can increase the inflammation that constricts the airways. Stress makes eczema worse, IBS worse.
After I had a flu that lasted for a solid 3 weeks, with a temperature recorded by the doctor if 41 degrees C, my brain became inflamed if I ate certain foods. Apparently if the microglia in the brain are activated, they don’t switch off.
So I have to be very careful what I eat otherwise my brain feels like it is heating up and burning.
That then has a terrible effect on my mental health, my memory and my ability to think and so on. I went to my doctor and said could you give me something for my brain inflammation and I think he thought I was just making it up or exaggerating. He did suggest I see a physiotherapist who tests for vertigo.
I have so many symptoms, if I set them off. They are frightening. I’m not saying my ideas are right, I’m just saying as a middle aged woman with immune issues, they seem to be working for me.
I agree that we are all so very different.
Absolutely. Consider that anxiety must push a dysregulated stress response even further into bad territory. Studies indicate that chronic sympathetic nervous system activation blunts our immune response to viruses! The SNS is an immune system regulator. Theoretically anxiety or hypervigilance – which is part of parcel of the fight or flight response – could, by causing more inflammation which further sensitizes pain receptors – could help produce quite a vicious circle!
That’s the position I felt I was in with this nagging cold. It became very clear to me that anxiety and worry was really exacerbating my symptoms! I’d always noted that to some extent – but never to this extent.
We so desperately need biomarkers and sub groups figured out. I have no doubt that there are some who will benefit from DNRS but not all. Personally my greatest improvement have been from taking the antiviral Valcyte.
We are all so complex and I really don’t believe in a one pill to fix all approach. There are far too many pieces to my puzzle and I’m sure that is true of others.
Hi Cort, I’d like to run a theory by you, if that’s ok. According to your summary in the article,
” Cortene proposed the novel idea that excessive levels of a receptor called CRF2 found on certain neurons in the brain were producing an unrelenting and hyperactive stress response in ME/CFS. Cortene believed that this improperly activated stress response was, in turn, responsible for the numerous downstream immune, metabolic and other issues that studies indicate are present in ME/CFS.”
I’ve recently investigated the efficacy of SGB (Stellate Ganglion Block) which seems to have a 70-75% success rate in treating PTSD!!
https://www.anxiety.org/stellate-ganglion-block-sgb-for-ptsd-research-update
So I hypothesize that the prolonged stress response in PTSD might have a similarity to Cortene’s theory of CFS (excessive levels of CRF2 producing unrelenting hyperactive stress response). I wonder since SGB treatment seems so effective for PTSD in turning off the stress response, if it might also be very effective for CFS patients (or at least a subset).
I personally have suffered with PTSD for many years. Healing from the trauma of horrific child abuse has been the hardest thing I’ve ever done and the intense stress of that process (nightmares, flashbacks, years of therapy, etc) I am convinced caused the CFS I’ve had for 22 years. It was in the course of investigating the SGB treatment that I thought perhaps what seems to be so effective for PTSD might possibly treat CFS as well.
Anyway, your thoughts would be appreciated, and as always thank you Cort for your great work with health rising and keeping the CFS community informed. Good luck to all of us and hopefully there will be an effective treatment before too long.
Thomas, I find that extremely interesting. Ive spent a few hours researching, and I like you strongly believe that its cPTSD, which resulted in CFS. But most importantly, is preventing recovery, in spite of all my significant efforts.
I have asked a couple of clinics for more information. Id be interested in your further thoughts or dialogue….? Best, Steve
For anyone reading… this was the first Ive heard of a Stellate Ganglion Block. However, I have long believed that cPTSD has ended up causing the CFS, and that CFS is an extreme ‘Freeze’ response of a tortured nervous system. Which I think totally correlates to the Dauer State CFS theory, and Polyvagal theory. In my case I think pushing against the PTSD has caused the CFS, which I appreciate may be considered a subtype, and that infections, extreme exercise etc… are also ways into this trap. However, I wonder if a stellate ganglion block could actually be an answer for CFS. The symptoms and reality of cPTSD fit me even better and more precisely than simply CFS fatigue. After intensive self reflection I do feel frozen. And not just psychologically. I totally think the brain, if you reject the strong mental freeze, simply disables your body, whether you like it or not. Hence all these biomarkers being found.
Anyway, Im rabbiting on, because having enquired in Chicago regarding SGB, I have found a single UK (where I am) pain clinic which also conducts the procedure. I intend to book in and have this done asap. I am warned it can take 2 or 3 treatments, which are not cheap, but anecdotally I see many PTSDers have responded very positively. And this could literally be a silver bullet.
I’m going to see….!
I think it’s Dr Nancy Klimas who says part of the immune system gets down regulated and part of it gets upregulated.
I believe my immune system had difficulty fighting off the flu virus I had and so my temperature went up to 41.
However I also now have asthma and extensive food intolerances (like most food) and can trigger interstitial cystitis, brain issues like poor memory, balance, mental health, inflammation, exhaustion, poor quality sleep, high blood pressure and heart rate and blurry vision and difficulty focusing my eyes, if I eat the ‘wrong”food. There’s more but I can’t remember it all. That’s enough anyway!
I think high levels of stress shuts down the digestive system and because my mind wants me to stay alert, in case of danger, I don’t sleep deeply/restoratively, which then affects the immune system, digestive system, my brain etc etc
Dr Nancy Klimas has a couple of videos called ME/CFS Treatment options Part 1 and Part 2.
They’re short and sensible. Dr Klimas is a level headed kind of person and because she’s aware of all the immune system issues, she makes sense to me.
Dr Klimas warns of the dangers of different treatments.
The last few months have been better for me, but before that over the last few years, everyday was like setting out across a frozen lake, where there were thin patches I didn’t know about. I was terrified of falling through these, to the water below.
I’ve had such bizarre symptoms that I’ve remembered: my sense of smell multiplied, so going anywhere was a nightmare as I thought it would set my asthma off. It actually didn’t and went after a few months. The skin on my knees and my left thigh went numb. That was related to what I was eating – nuts I think.
Losing the impulse to breathing in was one of the worst and having what I think were symptoms of very low blood sugar – feeling very cold, trembling, feeling dizzy, difficulty catching my breath were both caused by high levels of fructose.
I keep an eye on the diabetic information, as I have a problem with blood sugar, though I’m not diabetic. They are now finding that lack of sleep and food intolerances can trigger people into eating more sugary food, which can worsen their blood sugar control. Infection also causes mayhem with people’s blood sugar. My niece is Type 1 diabetic.
When I was ill in the beginning I noticed that when I ate sweet things it affected my brain, energy levels, depression, nausea etc. I went very pale. This was happening in my brain, I was aware of it.
I think something was happening in my liver (fructose has to be processed by the liver) and then something like insulin resistance was triggered in my brain.
I have a blood sugar monitor and it seems that when I eat something I’m intolerant to, it puts my blood sugar level up.
I had Glandular fever and I know it lingered on for decades because I always got swollen glands, if I was run down or I’ll. I thought that was normal.
I know Glandular fever affects the liver and I think it may have reactivated. I’ve read somewhere that it can make a base for itself in the vagus nerve, causing all sorts of problems.
Every time I have a certain kind of virus, I get this weird sort of nausea – like ribbons running down through my stomach/gut area. I thought everyone had that.
I know I’m peculiar, I’m just trying to manage it until a better alternative comes along.
I was a patient in the Cortene Trial. I received two infusion treatments on a Monday and Tuesday in late October, and then a third infusion in December. As of today, I am not sure how much I can speak yet about my experience. As a participant, I was asked not to speak about my experience until the results were published so I think that I can’t write about specifics, but after reading comments I also feel that the community deserves to know more. I would be happy to describe my experience and beliefs about what CT38 can and cannot do when I know that I’m permitted.
A couple of thoughts:
I do believe that CT38 is safe, and I would be willing to do another trial.
The Placebo Effect is a very powerful phenomenon, so we should always be cautious when drawing conclusions until there is a double-blind study. Nevertheless, I believe that I experienced a positive change that is somewhat independent of the placebo effect (something that can’t be faked and is measurable).
A drug can be beneficial and exciting by bringing symptom relief without actually curing ME/CFS.
I am currently most intrigued by the Metabolic Trap theory, and I have thought a lot about how Cortene’s hypothesis would fit in with this and other similar theories. It will be very interesting to read their published study.
I am now in my 5th year with ME/CFS. I am able to work, but I’m very limited in what I can do. I was able to do two CPET’s during the trial. In total, I would say that my health is no better today than I was at this time last year. However, there are some symptom areas that have improved, and I am very happy about for that. I do believe CT38 caused these improvements.
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Thanks Aaron
I think you delivered the news very well.
Thanks for providing your experience of it.
Aaron, I am glad you posted, I’ve wondered what is okay and not okay to say about the study. I’ve been sick 26 years, home bound most days. I’m a self proclaimed Batman guinea pig and have volunteered for many different trials through her office. The hardest part of the study was going off my Duloxetine to qualify. I am still sick, but have a measurable difference of some symptoms. I was excited to hear that I was the first patient to respond to one of the measurable differences. That measurable difference is still holding strong today! I wish I could have a few more doses of Cortene to see if other improvements would be possible.
I look forward to reading the paper. It seems to me that there is substantial sum to be made if this thing works. And there are enough venture/angel money sloshing around, they shouldn’t have too much difficulty raising fund if the first trial showed enough promise. As long as they make the deal interesting enough for investors, that is.
Cort,
You are so amazing. You are not a doctor or biomedical scientist, but have so much incredible knowledge, insight, memory, synthesis, and ideas about our illness. You also have such an incredibly great writing skill. I view your writing and see it as an example to reach. How fortunate we all are that you started and research and write HealthRising — keeping us all together “on one page” and helping us understand so much. And keep having hope.
Bless you,
Alden Lancaster
Just to comment on an above remark concerning ssri’s-I actually developed chronic fatigue syndrome from an ssri. Lexapro to be specific. I’ve always theorized that serotonin has a huge role to play in cfs.
I’ve spent a long time in the past 13 years of illness researching serotonin and receptors and effect on hpa axis and cortisol. So Cortene for me is very exciting! It’s nice to see focus shifting g from viruses and immune system to this. Yes I believe we have high viral loads and obvious immune regulation issues but from causes more related to the stress response.
If you look into ssri protracted withdrawals, and in the pssd (post ssri sexual dysfunction) community you will see a lot of us dealing with chronic fatigue due to ssri use.
Cort,
What is the best way to follow this process and stay informed on the progress of approval?
Also, any info on joining the next trial of the drug?
Thanks
Just stay subscribed to the blog. Cortene now needs to get a paper published and raise money for a bigger trial. That will take some time.
An update has been published with a few more details. This might be of interest https://cortene.wordpress.com/2020/01/
How do we participate in trials, and when can we get this in the uk?
@Cort,
any idea when Cortene will be releasing more info?
this probably will never make it to market because it will cure a handful of diseases cheaply and easily.
Hi Cort, I’ve only just come across this study area! The last update I could find was from January 2020, essentially saying ‘watch this space’
Have you heard anything more recent at all please?