Cortene Inc. está desarrollando un medicamento para SFC/EM

[Titiritero]

Parece que la empresa Cortene Inc. está desarrollando un medicamento para el SFC.

En la página web dicen que ya han realizado un estudio en fase 1 con sujetos sanos y que ahora planean realizar un estudio con el medicamento con afectados de SFC.

Os dejo el enlace a la página: http://corteneinc.com/

¿Alguien había oido algo sobre esto?

Un abrazo.

[coco]

https://www.healthrising.org/blog/2018/ ... s-soon-pt/

[Klass]

¡Gracias Titiritero y Coco! He estado leyendo el artículo de Cort y los comentarios a su post y me parece interesantísimo.

La hipótesis que trabajan los de Cortene tiene mucho sentido y no es nueva, ya Goldstein hablaba de esto en los años noventa. La diferencia es que estos investigadores parten de que creen que tienen el fármaco para resetear el sistema límbico y van a empezar a probarlo en enfermos.

Nos acercamos irreversiblemente al desenlace de esta pesadilla... por una vía u otra o la superposición de varias, ya veréis.

Un abrazo,
Klass
Un abrazo, nos acercamos

[omega]

Ojalá sea el fin ya de esta pesadilla

[crisis]

Aquí está el enlace a la parte 2


https://www.healthrising.org/blog/2018/ ... ypothesis/



Cortene II: A New Drug & A New Hypothesis For Chronic Fatigue Syndrome (ME/CFS)
healthrising.org/blog/2018/02/17/cortene-chronic-fatigue-syndrome-hypothesis/ By Cort Johnson
Part 1 introduced how Cortene became involved in chronic fatigue syndrome (ME/CFS), and introduced its hypothesis that a maladaptation within the limbic system, which shapes our response to stress, may underlie ME/CFS.
The Cortene Way: New Drug to Be Trialed in Chronic Fatigue Syndrome (ME/CFS) Soon – Pt. I
In Part II Health Rising takes a deeper dive into nuts and bolts under girding Cortene’s hypothesis.(Given the long nature of this post you may want to print the blog out using the print/PDF buttons on the bottom left hand side of the post)
Stress
“Stress” is an unfortunate term. Usually we think of stress as emotional; in biology, though, stress means any threat that disrupts the balance (or homeostasis) of the body. The stress response or HPA axis, prepares the body to respond to the threat. Any threat then, whether infectious, emotional, physical, chemical, etc, will initiate the stress response.
Once triggered, the stress response suppresses non-critical functions such as growth and metabolism (i.e., hypothyroidism, long linked to ME/CFS) and reproduction (i.e., hypogonadism, also connected with ME/CFS). It also releases cortisol to make sure the brain, heart and muscles have sufficient glucose (at the expense of less critical functions like digestion). Cortisol also primes the immune system for action (and has a delayed proinflammatory effect).
As noted in Part 1, studies indicate that chronic stress causes a progression from high to low cortisol and can result in the development of cortisol sensitivity – a situation in which the body becomes more responsive to cortisol. (When cortisol sensitivity occurs low cortisol can have the same or greater effects than high cortisol does in healthy individuals.) This increased cortisol sensitivity cannot be measured by cortisol/synacthen tests (which measure level not effect) but it does results from epigenetic changes that can be shown.
Studies indicate that ME/CFS patients show the same alterations in cortisol levels and cortisol sensitivity seen in chronic stress. These findings help to explain the overlap of immune and metabolic symptoms found in ME/CFS and chronic stress but they do not explain the neurological issues found in ME/CFS.
The stress response also involves brain neurotransmitters such as serotonin, norepinephrine, dopamine and GABA (gamma- aminobutyric acid), which focus on and deal with the stress in a
Cortene’s new hypothesis for ME/CFS will shortly be tested in a small exploratory drug trial
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stressor-specific way. These neurotransmitters – which may
have been under-appreciated in ME/CFS research – are at the core of Pereira’s hypothesis.
Animal studies indicate that short, medium and long term responses to stress are governed by two factors, CRF (corticotropin-releasing factor) and UCN1, that affect the release of serotonin (and norepinephrine) in the brain and cortisol (and epinephrine) from the adrenal glands.
If these two factors do indeed govern the response to stress in humans, Pereira/Cortene believe that if they can get at the switch controlling them they can reset the stress response system. That can be achieved they believe by altering the receptors found on the neurons that govern the stress response.
Some background...
The Players
Corticotropin-releasing factor (CRF or CRH) is a hormone produced in response to stress that initiates and shapes the stress response. It has two receptors it can bind to on neurons: CRF1 and CRF2.
Receptors are proteins on the surface of a cell which make it possible for the cell to respond to its environment. When molecules lock onto receptors they trigger actions in the cells –such as the production of hormones, neurotransmitters, cytokines, etc.
Cells don’t just respond to their environment, however. By altering the kind and number of receptors on their surface they determine the kinds of response that are possible.
As we’ll see, cells often prime themselves for one type of action by loading their surface with one type of receptor. In the scenario below, different levels of stress; i.e. different levels of CRF, have very different effects on two receptors found on stress response neurons.
Depending on how much of the stress hormone CRF is present one or another receptor will dominate the surface of our stress response neurons. Each of those receptors, in turn, will have very different effects on how much serotonin those neurons will produce. Keep your eye on serotonin in the following scenario
Low Stress States (CRF1) – Low levels of stress (low CRF) activate CRF1 receptors on GABA-releasing neurons of the raphe nuclei and limbic system, triggering the release of GABA, which decreases serotonin release in the limbic system. During low levels of stress, then, CRF acts via CRF1 to inhibit serotonin. (The CRF1 receptor, then, inhibits serotonin.)
High Stress States (CRF2) – High levels of stress (high CRF), cause the CRF1 receptors to leave the surface (or internalize) on GABA-releasing neurons and bring CRF2 receptors to the surface of serotonin-releasing neurons. During intense stress, CRF acts via CRF2 to pound out serotonin. (CRF2, then, increases serotonin.)
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Urocortin 1 (UCN1) – UCN1 is a peptide that interacts with CRF1 and CRF2. When the stress dissipates, UCN1 causes the CRF2 receptors to internalize in the serotonin-releasing neurons, and the system returns to baseline. UCN1, then, normalizes the stress response.
A Dysfunctional System Appears Step I: Serotonin Release
Serotonin is the bogeyman in this hypothesis. In the brain, serotonin is produced by the raphe nuclei in the brain stem, and serotonin neurons extend throughout the limbic system (including the hypothalamus) and the prefrontal cortex, affecting all the other neurotransmitters and coordinating the response to stress.
Step II: Desensitization
The raphe nuclei and limbic system shape the stress response (by incorporating assessments of risk, reward, history, etc), but under intense stress they can desensitize the 5HT1A autoreceptors that normally halt the stress response – allowing it to run amok. Pereira/Cortene believe this is what is happening in ME/CFS.
No stimulatory part of the body is ever designed to be “on” all the time. Because stimulating any system for too long will cause it to break down, any stimulating response comes equipped with brakes. The brakes on an out-of-control serotonin response in the brain are the 5HT1A serotonin autoreceptors. (“Auto” meaning that when these receptors sense serotonin around a particular neuron, they reduce that neuron’s release of serotonin).
Studies in both animals and ME/CFS patients suggest that riding the serotonin stress- response system for too long causes the 5HT1A “brake” to fail and the 5HT1A autoreceptors become desensitized.
With that the foundation of this hypothesis is complete.
Step III: Chronic Fatigue Syndrome (ME/CFS) Begins
In situations of intense stress (e.g., infection, trauma, emotional distress), high levels of CRF in the raphe nuclei (and limbic system) propel serotonin promoting CRF2 receptors to the surface of serotonin producing neurons. The high levels of serotonin produced cause the 5HT1A “brake” to fail. Once that happens, high serotonin levels prevent the release of UCN1 and the re-establishment of homeostasis.
Serotonin producing neurons and serotonin play key roles in Peireira’s hypothesis.
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UCN1, remember, causes the serotonin promoting CRF2 receptors to disappear back into the neuron. With UCN1 unable to return the system to normality, the CRF2 receptors remain on the neuron’s surface – telling it to keep pumping out serotonin.
With the neurons (in the raphe nuclei and limbic system) now packed with serotonin- producing receptors (CRF2), and the brakes on serotonin release gone (desensitized 5HT1A autoreceptors), the HPA axis has become sensitized. Now even minor stressors, like exercise or emotional stress, or even stimulation (light, sound, conversation) can initiate a major stress response. This is what Pereira/Cortene believe is happening in ME/CFS (and probably in related diseases such as fibromyalgia).
Animal studies demonstrate how this progression occurs. Intense or prolonged stress (particularly early in life) causes CRF2 receptors to remain on the surface of the neurons long after the triggering stress has gone causing 5HT1A desensitization and behavioral issues (impaired memory and learning ability, anxiety, PTSD-like behavior).
There is hope for these animals, however. Removing the serotonin promoting CRF2 receptors (via sophisticated experimental techniques) eliminates the 5HT1A desensitization and the behavioral issues.
Consequences of Excess Serotonin
If ME/CFS patients’ brains have been turned into serotonin pumping machines, what causes the immense fatigue and post-exertional malaise found in this disease?
It turns out that serotonin plays a vital role in the motor cortex and spinal cord as well. At low levels, it increases motor neuron excitability, making the muscles more responsive. As activity increases, serotonin levels increase, and the motor neurons/muscles become even more responsive.
However, when serotonin levels become too high, they inhibit motor neuron signals, preventing muscle contraction (to avoid muscle damage). Several studies suggest that reduced motor cortex excitability, motor preparation, motor performance and central activation during exercise may be present in ME/CFS.
Pereira/Cortene believe that the hypersensitive serotonin response in ME/CFS patients causes them to reach this threshold very quickly. Intriguingly, their hypothesis also may illuminate an unusual experience that many people with ME/CFS may feel: that their
Peireira’s hypothesis proposes a way even minor stressors can produced major stress reactions in the body in ME/CFS
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muscles feel more like they’re stuck or paralyzed than that they’ve have run out of energy – and that any stimulation can make the situation worse.
Increases in serotonin have been directly implicated in increased pain sensations, cognitive dysfunction, migraine, sensitivities (light, sound, etc.), sleep dysfunction and depersonalization. Indirectly, by stimulating other neurotransmitters such as dopamine and norepinephrine, serotonin regulates everything from behavior (e.g., mood, perception, reward, anger, aggression, attention, appetite, memory, sexuality) to physiology (e.g., gastrointestinal functioning, blood coagulation, blood pressure, heart rate).
But why have these postulated CRF2/CRF1 maladaptations not shown up in the ME/CFS research to date? Tests of blood and other bodily fluids will not pick up a problem existing only on specific neurons in the brain. Nor can the serotonin output of these specific neurons be measured. While cerebrospinal fluid can get close, it lacks the precision to identify a problem involving a tiny subset of neurons in the brain. Biopsies of specific neurons in the raphe nuclei and limbic system in the brain are needed.
Some indirect evidence does suggest that this hypothesis may be correct. The limbic system neurons postulated by Pereira/Cortene to be problematic are, in fact, the same brain regions that light up in Nakatomi’s ME/CFS work. Cleare’s 2005 pet scan study indicates 5HT1A autoreceptors are desensitized across the entire limbic system in ME/CFS; and Maes has found antibodies to serotonin in ME/CFS patients’ blood.
Of course, there’s more to ME/CFS than altered brain chemicals.
How does this hypothesis account for the hypometabolism seen by Naviaux, Armstrong, Fluge and Mella and Davis?
The Pereira/Cortene hypothesis proposes that a sensitized HPA axis causes even small stresses (including the disease itself) to release cortisol into a system with increased cortisol sensitivity. The resulting excess of cortisol stimulation creates insulin resistance, a situation where the normal insulin-directed uptake of glucose by cells is inhibited by cortisol.
The result is increased blood levels of both insulin and glucose, shown to be present in ME/CFS patients (Armstrong/McGregor). Elevations in insulin and glucose in ME/CFS serum could also explain Ron Davis’s work, in which healthy cells become abnormal in ME/CFS serum but remain normal with the addition of pyruvate (which reduces insulin resistance in animals). The resulting lack of glucose in ME/CFS cells could also explain why these cells appear to be using non-glucose substrates (Naviaux, Fluge and Mella).
What about the Immune System?
The notion of a sensitized HPA axis could also help explain the immune dysfunction found in ME/CFS. Cortisol has both an initial anti-inflammatory effect and a delayed pro- inflammatory effect which is intended to deal with any injury arising from the stress. In chronic stress, however, excessive cortisol stimulation suppresses Th1 (cellular immunity)
Peireira believes his hypothesis could account for the low energy states studies have found.
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and promotes Th2 (humoral immunity), with attendant changes in cytokines. This could explain why ME/CFS patients are prone to both allergies (driven by increased Th2) and opportunistic infections (driven by decreased Th1). Note also, that under certain circumstances, a corticosteroid (which is essentially a cortisol mimic) could worsen an ongoing stress response and worsen ME/CFS.
Other Symptoms?
A sensitized HPA axis would also result in excess norepinephrine (NE) release potentially explaining many of the autonomic symptoms found in ME/CFS, such as a high resting heart rate, low heart rate variability, low blood pressure and orthostatic intolerance, and abnormalities of the gastrointestinal system (potentially leading to leaky gut) and urinary system.
What about the four facets of the disease (mentioned in Part 1)?
Diverse triggers: Any stress, e.g., infection, emotional distress, physical trauma, chemicals, could result in the postulated CRF2/CRF1 maladaptations. A sudden outbreak of ME/CFS would likely be due to a single pathogen sweeping an area. Plus, Hickie found in the Dubbo studies that different infectious triggers cause post-viral fatigue in ~11% of cases. The fact that those with the most intense immune response (i.e., greatest symptoms) tended to come down with ME/CFS, suggests that for the known infectious triggers, an underlying natural, likely genetic, proclivity to the development of ME/CFS exists (see below).
Sudden/gradual onset: Over time accumulated CRF2/CRF1 maladaptations could result in a sensitized HPA axis. This could happen via an intense stress sufficient to produce maladaptation (sudden onset), or the accumulation of sub-threshold stresses over time (gradual onset).
Gender bias: The female stress response releases more CRF than does the male, has more CRF1 and CRF2 receptors overall, has greater concentrations of CRF1 and CRF2 in certain parts of the limbic system, and shows reduced rates of CRF1 and CRF2 internalization. Other differences exist as well, but all point in a direction that heightens the female response to stress. Importantly, many of these differences emerge at puberty, which explains why the gender bias in ME/CFS is only evident post-puberty (i.e., no gender difference pre-puberty).
Symptom range and variability: Animal work has shown that stress-based adaptations are stressor-specific and result in different maladaptations in the limbic system. This suggests that the symptom presentation of a given ME/CFS patient depends on that patient’s cumulative stress history. This could explain how some patients can present with primarily physical symptoms while others have primarily cognitive symptoms. The symptoms vary over time because the level of the HPA axis response is affected by whatever stress the patient might be under at the time of measurement. This explains why some patients are able to reduce their symptoms with meditation and other calming
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techniques while some are not. It also explains why putting patients under stress (e.g., via CPET or cardiopulmonary exercise testing) improves the consistency of study results in ME/CFS.
Other Evidence
The risks of developing ME/CFS, and increased symptom severity after one has ME/CFS, have been associated with a wide range of genes involved in the HPA axis and serotonin. That list includes CRF2, CRF1, TPH2 (involved in serotonin synthesis), 5HTT (the serotonin transporter), NR3C1 (the cortisol receptor), POMC (a precursor for ACTH, which triggers the release of cortisol under stress), and TH and COMT (both involved in dopamine, epinephrine and norepinephrine synthesis/breakdown).
Note that all of these genes are involved in the stress response. Defects in them could either make it difficult to unwind or tamp down an ongoing stress response or result in a hypersensitive stress response. Either of those situations could lead to the loss of the 5HT1A “brake” described in Pereira’s hypothesis, and potentially explain the Dubbo findings.
Finally, Peireira’s hypothesis has something to say regarding the mixed effects SSRI antidepressants have on people with ME/CFS. Neurons communicate via neurotransmitters (such as serotonin) jumping the gap between them. SSRIs work by blocking the serotonin transporter (a channel in the neuron that recycles serotonin in the gap). This was proposed to solve depression by increasing what was thought to be low serotonin.
In fact, depression is caused by high serotonin releases from specific neurons. Blocking the serotonin transporter, causes serotonin to build up outside these neurons until, 2-8 weeks later, it triggers 5HT1A auto-regulation which reduces these neurons’ release of serotonin.
The trouble is that SSRIs block the serotonin transporters on all neurons. This means SSRI will eventually reduce serotonin from neurons releasing excess serotonin (via auto- regulation), but it will also increase serotonin release everywhere else (just not to a level that triggers auto-regulation). This is what causes the many side-effects of the SSRIs— and, notably, these are the symptoms of ME/CFS.
This long overview suggests that Pereira/Cortene’s hypothesis could explain much of what’s happening in ME/CFS. But is there evidence that turning down CRF2 receptor activity as they propose could work?
In Part 3 we’ll dig into that question and describe the upcoming clinical trial.
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Genetic studies suggest Cortene may be looking in the right area
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La hipótesis parece brillante. Ya veremos.

Saludos

[Esteban976]

Incluso aunque fuera bien...los plazos de aplicación de medicamentos no rondan los 5 años?

[Dandelion]

Y si tiene que llegar a España... ni te cuento, pero vamos... que si hay que cruzar el charco, se hace
¡vuelo charter de SFC/EM! ¿os imagináis?

[Esteban976]

Jeje...me apunto. Si funciona, lo que sea. Pero no espero ni un mes

[coco]

Incluso aunque fuera bien...los plazos de aplicación de medicamentos no rondan los 5 años?

Entre una cosa y otra échale diez.

[Esteban976]

Jodopetaca. Para entonces igual tengo Alzheimer y no recuerdo que estoy enfermo...

[Klass]

Jajaja

¡Qué grandes sois! Con la que tenemos encima y cómo os tomáis todo... me encanta.

Fletar un avión me parece una gran idea... o pensamos a lo grande o no hacemos nada. ¡Qué host--s!

A ver qué nos cuenta Cort en la tercera parte del artículo

[crisis]

Esta es la primera parte


The Cortene Way: New Drug to Be Trialed in Chronic Fatigue Syndrome (ME/CFS) Soon – Pt. I
healthrising.org/blog/2018/02/08/cortene-way-new-drug-trialed-chronic-fatigue-syndrome-mecfs-soon-pt/
By Cort Johnson
Research funding for chronic fatigue syndrome (ME/CFS) has been poor at best but clinical trials have elicited a wholly different degree of disappointment altogether. Few clinical trials are ever done and those often involve alternative approaches. The six active clinical trials listed in clinicaltrials.gov, for instance, include treatments like acupuncture, moxibustion, oral rehydration and CoQ10.

That makes it shocking to see a “new” drug – a drug not being used in other diseases – get a clinical trial in ME/CFS. It wasn’t supposed to happen this way. First, it’s been assumed that repurposed drugs – drugs already in use in other disease – would be tested in ME/CFS to improve symptoms – and only later, as we understood the disease better, would we get to a drug that gets at the core problems in ME/CFS. This group believes they have a drug that gets at the core of ME/CFS now, and in the first quarter of this year they expect to test that drug.

Over the next month, Health Rising will be publishing a 3 or 4-part blog series telling the story of the small group of researchers that are bringing a drug to ME/CFS they believe could get at the core of this disease.

The drug itself is highly experimental and the researchers behind it come from the biotechnology and drug development fields. They stumbled on ME/CFS by chance, but when they did, the light bulbs went on. For the past year or two, they’ve devoted their time to understanding ME/CFS and getting to the place where a clinical trial can take place.

IV bottle
Rather shockingly, a new drug – a drug not being used in any other disease – will soon be tested in ME/CFS.
It’s important to realize that these researchers/investors – like all good researchers/investors – are essentially agnostic regarding which disease to test their drug in. They’re fully aware of the history of neglect in ME/CFS and my sense in talking to them is that that neglect, and the opportunity to provide help to such an underserved community excites them.

Their decision to spend the time, money and effort to test this drug in chronic fatigue syndrome is not because of the great need ME/CFS patients are in, but because this is the disease they believe this drug will work in. In order to come to that conclusion, they’ve explored ME/CFS very carefully.

The upshot of this very different approach (for us anyway) is that, while this drug is new, it probably enjoys a more robust theoretical foundation than any other drug that’s been tested in ME/CFS. That provides, at least for me, some reason for hope.

The group has flown under the patients’ radar but have not hid their light under a bush. Over the past year they’ve conducted an impressive outreach program – a kind of learning and enrolling tour – communicating with several major ME/CFS doctors and researchers across the country. None, they report, have been able to find any flaws in their hypothesis and all agree that their drug should be tested. The trial is expected to take place in the first quarter of this year at a well-known ME/CFS expert’s clinic. (The details of the trial will be released in the last blog.)

The upshot is that to virtually everyone’s surprise, a new and experimental drug will soon be tested in chronic fatigue syndrome (ME/CFS). It’s a fascinating story. Enjoy…

Part I – Beginnings and the Hypothesis
Part II – The Hypothesis Pt. II
Part III – Treating ME/CFS and the Clinical Trial
A New Hypothesis on the Cause of ME/CFS – Part 1/3
Gerard Pereira didn’t know much about chronic fatigue syndrome (ME/CFS) but what he was hearing was setting off all sorts of bells and whistles in his head. Sometime before, he’d come across an intriguing drug (CT38) being developed by the pharmaceutical division of Proctor & Gamble. CT38 prevented muscle wasting in animals, and it had been through a Phase 1 clinical trial and tested safe in healthy humans.

Despite the promising test results, after Proctor & Gamble decided to exit the drug industry entirely, CT38 was left available for licensing.

Pereira had been tasked with finding promising new drugs and he liked this one. Despite strong animal data, though, Pereira’s employer wasn’t interested. The commercial potential, they felt, just wasn’t there. One population CT38 might help (people on mechanical ventilators) was hard to study and short in supply. A chronic disease like muscular dystrophy might fit the bill, but would require big money for long-term animal safety studies.

Pereira, though, was intrigued. CT38 targeted the stress response – a system getting a lot of attention, and it appeared to impact inflammation – a bigger and bigger concern all the time. Plus, the animal data was really good. Eventually Pereira decided to license the drug and start his own company, Cortene Inc. He and his partners (Sanjay Chanda, Hunter Gillies, Michael Corbett) would try to develop the drug themselves.

Pereira was at a cocktail party discussing his drug with a well-known Stanford doctor, who was talking about some immune findings in a strange disease called ME/CFS. Pereira had not heard of the disease before, but the immune findings, and ME/CFS in general, seemed eerily reminiscent of the data he’d seen produced for CT38.

explaining chronic fatigue syndrome
How to explain the rapidity with which ME/CFS often comes became a key question for Peireira.
Pereira took a deep dive into the ME/CFS literature. The more he saw, the more he liked the fit. He was particularly taken by four facets that seemed to separate ME/CFS from other diseases: the diversity of the apparent triggers, the unusual suddenness with which the disease often appeared, the gender imbalance, and the wide range and variability of symptoms – both across patients and over time. Explaining those four facets, he thought, might lead to the cause of the disease. Most of the current hypotheses couldn’t. Could he?

Take the idea that a pathogen or an immune system issue was the key culprit. Could either explain how a healthy person – often a female – could be turned into an invalid, sometimes overnight? He didn’t think so. Too many different pathogens had been connected to ME/CFS for one pathogen to do it, and pathogens usually affected both genders equally. Plus, no one had been able to definitively show a pathogen was still present and/or still responsible for the symptoms seen in the chronic phase of ME/CFS.

The immune system was certainly involved, but the patient stories he’d heard suggested that the disease happened too fast for the big guns of the immune system – which took time to get worked up – to take down a patient so suddenly. Too many people with ME/CFS caught a cold, and then were suddenly floored by the illness, for that to make sense. He didn’t think the metabolic ideas sweeping the field fit the bill either. Metabolic changes were certainly present, but a rapid metabolic breakdown that happened predominately in females was hard to explain.

Instead, he thought the initial insult (infection, stress, etc) must have caused changes in some integral system; a system able to touch the immune and autonomic nervous systems and ultimately even glucose metabolism .

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An adaptation (or perhaps maladaptation) of the limbic system that determines our responses to stressors like infection, trauma, emotional distress, etc., could fit the bill. The limbic system had been considered in ME/CFS for decades, but no one had ever proposed a drug for it.

A change to the stress receptors governing those responses could happen very quickly. When it did, Pereira thought it would push the immune system in exactly the way it’s showing up in ME/CFS – and impair patients’ ability to fight off infection. That made sense given the Dubbo study reports that more severe, difficult to fight off infections, tend to trigger ME/CFS. It could also affect the autonomic nervous system, and eventually impact the glucose metabolism. The more he looked, the more he liked the idea that alterations to the stress receptors in the limbic system could explain ME/CFS. These were the same stress receptors that CT38 was designed to work on.

The HPA axis received a good deal of study in ME/CFS early on, but the results weren’t always consistent, and interest had waned somewhat over time. Still, the axis had a way of popping up. Gordon Broderick’s models suggested issues with the HPA axis could explain the gender imbalance in ME.CFS, and Dr. Bateman had proposed that ME/CFS might be an inflammatory disorder centered on the hypothalamus. Just a month ago, a study suggested an immune-neuro-endocrine interaction might be causing the fatigue in ME/CFS.

A Mystery No Longer? The Big Picture Emerging In Chronic Fatigue Syndrome? Dr. Bateman Talks

The main endocrine finding in ME/CFS was low cortisol (hypocortisolism). Hypocortisolism also occurs in chronic stress, where the initial excess of cortisol becomes low cortisol over time – and the development of something like cortisol sensitivity.

Pereira thought the HPA axis might be able to explain the gender imbalance issues as well. Women have more stress receptors than men, and another part of the hypothesis (covered in the next blog) fits women particularly well. Because the stress response is intended to take control and divert resources to/from critical/non-critical functions, it impacts most of the systems in the body. All in all, Peireira thought HPA axis issues could explain the wide range of symptoms in ME/CFS.

Long-Term Illness – Short-Term Treatment?
There was still the long-term animal safety data problem, though. CT38 had been developed initially for short-term use and gathering long-term animal safety data would be prohibitively expensive. How could a drug with short-term animal safety data be applied to a chronic, often life-long, illness like ME/CFS?

recovery
Cortene hopes its drug can quickly reset the core problem in ME/CFS.
Now comes the most intriguing and exciting part of Pereira’s hypothesis. Pereira doesn’t need long-term animal safety data because he doesn’t plan on doing long-term treatments. If his hypothesis is correct, he believes CT38 will be able to reset the limbic system almost as quickly as it fell off the tracks in the first place; i.e., a couple of treatments might be enough to return the system to normal and begin the healing process.

If the idea of a more or less instantaneous reversal after decades of illness seems like some sort of fairy tale, consider that Suzanne Vernon and Gordon Broderick proposed something similar about ten years ago. Their model suggested that an HPA axis reset – by dramatically lowering cortisol levels for a short period of time – could cause the system to spontaneously reset.

This is not to say that over time other medical issues haven’t shown up in some ME/CFS patients that could complicate their situation. That’s to be expected in any decades long disease. If Pereira and Cortene are right, though, the core of this disease might be amenable to a dramatic change.

Part 2 will examine Cortene’s hypothesis in greater detail and show how it attempts to explain the many symptoms and anomalies of ME/CFS. Part 3 will explain the treatment approach and provide details on the upcoming clinical trial. (Health Rising is not affiliated with Cortene in any manner.)

To sum up – With the help of a physician, well-known within the ME/CFS community, Cortene will be conducting a small proof-of-concept trial, at a single site in the US. The details will follow, but the trial design is intended to obtain a rapid, objective assessment of their drug, and they will release the data as soon as possible. They reiterate that this is early-stage research and that caution is appropriate.

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[Sanat Kumara]

¡Gracias Titiritero y Coco! He estado leyendo el artículo de Cort y los comentarios a su post y me parece interesantísimo.

La hipótesis que trabajan los de Cortene tiene mucho sentido y no es nueva, ya Goldstein hablaba de esto en los años noventa. La diferencia es que estos investigadores parten de que creen que tienen el fármaco para resetear el sistema límbico y van a empezar a probarlo en enfermos.

Nos acercamos irreversiblemente al desenlace de esta pesadilla... por una vía u otra o la superposición de varias, ya veréis.

Un abrazo,
Klass
Un abrazo, nos acercamos

Estoy de acuerdo contigo.Y Jay Golstein fué un genio incomprendido y ademas en aquella epoca no existian los avances que existen ahora en genetica y en metabolonica pero esta teoria es la más completa y explica perfectamente la mayor parte de sintomas de nuestra enfermedad con la salvedad de que ahora si existen las herramientas para descubrir cual es la diana y que flecha usar cosa que no existia en la epoca de Goldstein.

La hipotesis de la disfunción limbica la apoyan otros grandes especialistas como el doctor Paul Cheney.En España Joaquin Fernandez Solá del Clinic y tambien esta hipotesis entronca con la que explica el porqué el metodo Gupta funciona parcialmente en bastantes enfermos.

En fin,que yo tambien estoy ilusionado y es esta una sensación que desconocia dese hacia muchos años por desgracia.

[Klass]

@Sanat Kumara Esta vez estamos totalmente de acuerdo

Estaría bien que alguno de los compañeros médicos, biólogos, veterinarios y demás ramas leyeran la segunda parte del artículo de Cort a ver si ven alguna incongruencia en la hipótesis de los del Cortene, porque lo que es yo... me suena todo coherentísimo.

Un abrazo,
Klass

[Esteban976]

Me he leído hasta la mitad, sin entender nada. Luego me he percatado de que no estaba en español...pero bueno, esperemos que sea algo bueno...

[Esteban976]

El humor me mantiene en pie, Klass...jeje

[Klass]

Jajaja, anda quéeeeee...

A ver si me dejan un rato tranquila y hago un resumen de los post en castellano.

@Es@Esteban976 pues sigue así, que no es poco lo de que te mantenga... además si al final el hipotálamo es el núcleo central de todos nuestros males... el buen sentido del humor pasa a ser terapia oficial para nosotr@s

[crisis]

A ver si me dejan un rato tranquila y hago un resumen de los post en castellano.

Vale si haces tú un resumen en castellano, no hago la traducción completa. Lo estuve revisando y hay palabras de difícil traducción.

Quería comentaros que en el foro de Health Rising interviene Cort Jonhson diciendo dos cosas que a mí me han puesto por las nubes

- los ensayos en humanos (enfermos de SFC) tardarán de 1 a 2 años

- que si el resultado es positivo van a acelerar la aprobación por la FDA, como en el caso del Ampligen

- esta ya es una precisión mía: es posible importar fármacos aprobados en EEUU antes de su aprobación en España.

No quiero echar las campanas al vuelo, pero si Cortene funciona estamos más o menos a unos 3 años de tener el remedio¡¡¡¡TRES AÑOS!!!!

Cort Jonhson también dice en el foro que si un paciente empieza a tomar Cortene en meses ¡¡¡MESES!!!! estaría curado.

Me gustaría no emocionarme ni ponerme eufórica porque otros ensayos de fármacos ya han fracasado. La hipótesis de Cort podría no ser tan correcta y brillante, pero no puedo dejar de emocionarme. Sobre todo los severos que no pierdan la esperanza, estamos cada vez más cerca de la solución.

Emocionados saludos a todos

[Klass]

@crisis Pues iba a hacer un resumen a partir de una traduccion mala (Google Translate) que he hecho con el móvil en el rato de la comida... y lo haré pero de momento cuelgo esa traducción que en general, se entiende:

Los fondos de investigación para el síndrome de fatiga crónica (EM / SFC) han sido pobres en el mejor de los casos, pero los ensayos clínicos han provocado un grado completamente diferente de desilusión. Pocos ensayos clínicos se realizan alguna vez y con frecuencia implican enfoques alternativos. Los seis ensayos clínicos activos enumerados en clinicaltrials.gov, por ejemplo, incluyen tratamientos como acupuntura, moxibustión, rehidratación oral y CoQ10.

Eso hace que sea sorprendente ver un medicamento "nuevo", un medicamento que no se usa en otras enfermedades, obtener un ensayo clínico en EM / SFC. No se suponía que sucediera de esta manera. En primer lugar, se ha supuesto que los fármacos reutilizados (medicamentos que ya se usan en otras enfermedades) se evaluarían en EM / SFC para mejorar los síntomas, y solo más tarde, a medida que entendiéramos mejor la enfermedad, obtendríamos un medicamento que se administra problemas en ME / CFS. Este grupo cree que ahora tienen un medicamento que se encuentra en el núcleo del ME / CFS, y en el primer trimestre de este año esperan probar ese medicamento.

Durante el próximo mes, Health Rising publicará una serie de blogs de 3 o 4 partes que contarán la historia del pequeño grupo de investigadores que están llevando un medicamento a EM / SFC que creen que podría ser el centro de esta enfermedad.

El medicamento en sí es muy experimental y los investigadores que lo respaldan provienen de los campos de desarrollo de la biotecnología y las drogas. Tropezaron con ME / CFS por casualidad, pero cuando lo hicieron, las bombillas se encendieron. Durante el último año o dos, han dedicado su tiempo a comprender ME / CFS y llegar al lugar donde se puede llevar a cabo un ensayo clínico.

importante darse cuenta de que estos investigadores / inversionistas -como todos los buenos investigadores / inversores- son esencialmente agnósticos con respecto a qué enfermedad probar su medicamento. Son plenamente conscientes de la historia de negligencia en EM / SFC y mi sentido al hablarles es ese descuido y la oportunidad de brindar ayuda a una comunidad tan marginada los entusiasma.

Su decisión de invertir el tiempo, dinero y esfuerzo para probar este medicamento en el síndrome de fatiga crónica no se debe a la gran necesidad de pacientes con EM / SFC, sino porque esta es la enfermedad en la que creen que funcionará este medicamento. a esa conclusión, han explorado ME / CFS con mucho cuidado.

El resultado de este enfoque tan diferente (para nosotros de todos modos) es que, si bien este medicamento es nuevo, probablemente tenga una base teórica más sólida que cualquier otro medicamento que se haya probado en EM / SFC. Eso proporciona, al menos para mí, algún motivo de esperanza.

Una nueva hipótesis sobre la causa de ME / CFS - Parte 1/3

Gerard Pereira no sabía mucho sobre el síndrome de fatiga crónica (EM / SFC), pero lo que estaba escuchando era provocar todo tipo de campanas y silbidos en su cabeza. En algún momento antes, se encontró con un fármaco intrigante (CT38) desarrollado por la división farmacéutica de Procter & Gamble. La CT38 evitó el desgaste muscular en animales, y se realizó a través de un ensayo clínico de Fase 1 y se probó con seguridad en humanos sanos.
A pesar de los prometedores resultados de las pruebas, después de que Procter & Gamble decidiera salir por completo de la industria farmacéutica, CT38 quedó disponible para licencia.

A Pereira se le había encomendado la tarea de encontrar nuevas drogas prometedoras y le gustaba esta. Sin embargo, a pesar de los datos en animales, el empleador de Pereira no estaba interesado. El potencial comercial, sentían, simplemente no estaba allí. Una población CT38 podría ayudar (personas con respiradores mecánicos) era difícil de estudiar y de poco suministro. Una enfermedad crónica como la distrofia muscular podría encajar en la factura, pero requeriría mucho dinero para estudios de seguridad animal a largo plazo.

Pereira, sin embargo, estaba intrigado. CT38 se centró en la respuesta al estrés, un sistema que llama mucho la atención, y parecía tener un impacto en la inflamación, una preocupación cada vez más grande todo el tiempo. Además, los datos de los animales fueron realmente buenos. Eventualmente, Pereira decidió licenciar el medicamento y crear su propia compañía, Cortene Inc. Él y sus socios (Sanjay Chanda, Hunter Gillies, Michael Corbett) tratarían de desarrollar el medicamento ellos mismos.

Pereira estaba en un cóctel discutiendo su droga con un conocido médico de Stanford, que estaba hablando de algunos hallazgos inmunes en una extraña enfermedad llamada ME / CFS. Pereira no había oído hablar de la enfermedad antes, pero los hallazgos inmunes, y ME / CFS en general, parecían inquietantemente reminiscentes de los datos que había visto producidos para CT38.

Pereira profundizó en la literatura de ME / CFS. Cuanto más veía, más le gustaba el ataque. Fue particularmente atrapado por cuatro facetas que parecían separar ME / CFS de otras enfermedades: la diversidad de los factores desencadenantes aparentes, la rapidez inusual con que la enfermedada menudo aparecieron, el desequilibrio de género y el amplio rango y la variabilidad de los síntomas, tanto entre los pacientes como a lo largo del tiempo. Explicar esas cuatro facetas, pensó, podría conducir a la causa de la enfermedad. La mayoría de las hipótesis actuales no podrían. ¿Podría el?
Tome la idea de que un patógeno o un problema del sistema inmune fue el culpable clave. ¿Podría explicar cómo una persona sana, a menudo una mujer, puede convertirse en inválida, a veces de la noche a la mañana? Él no lo creía. Se habían conectado demasiados patógenos diferentes a ME / CFS para que un patógeno lo hiciera, y los patógenos generalmente afectaban a ambos géneros por igual. Además, nadie había sido capaz de demostrar definitivamente que un patógeno todavía estaba presente y / o aún era responsable de los síntomas observados en la fase crónica de EM / SFC.

El sistema inmunitario ciertamente estaba involucrado, pero las historias de pacientes que había escuchado sugerían que la enfermedad sucedía demasiado rápido para que las grandes armas del sistema inmune -que tardaron en ponerse nerviosas- para abatir a un paciente tan repentinamente. Demasiadas personas con ME / CFS contrajeron un resfriado, y luego de repente se sintieron abatidas por la enfermedad, para que eso tuviera sentido. Tampoco creía que las ideas metabólicas que abarcaban el campo se ajustaran a la ley. Los cambios metabólicos estaban ciertamente presentes, pero una interrupción metabólica rápida que ocurrió predominantemente en las mujeres era difícil de explicar.

En cambio, pensó que el insulto inicial (infección, estrés, etc.) debe haber causado cambios en algún sistema integral; un sistema capaz de tocar el sistema nervioso autónomo e inmune y, en última instancia, incluso el metabolismo de la glucosa.

Una adaptación (o tal vez mala adaptación) del sistema límbico que determina nuestras respuestas a los factores estresantes como infección, trauma, angustia emocional, etc., podría encajar. El sistema límbico había sido considerado en ME / CFS durante décadas, pero nadie había propuesto un medicamento para ello.

Un cambio en los receptores de estrés que rigen esas respuestas podría suceder muy rápidamente. Cuando lo hizo, Pereira pensó que impulsaría el sistema inmunitario exactamente de la misma forma en que aparece en ME / CFS, y perjudicaría la capacidad de los pacientes para combatir las infecciones. Eso tenía sentido dado que el estudio de Dubbo informa que infecciones más severas y difíciles de combatir, tienden a desencadenar EM / SFC. También podría afectar el sistema nervioso autónomo y eventualmente afectar el metabolismo de la glucosa. Cuanto más miraba, más le gustaba la idea de que las alteraciones de los receptores de estrés en el sistema límbico pudieran explicar ME / CFS. Estos fueron los mismos receptores de estrés que CT38 fue diseñado para trabajar.
El eje HPA recibió una gran cantidad de estudio en ME / CFS desde el principio, pero los resultados no siempre fueron consistentes, y el interés había disminuido un poco con el tiempo. Aún así, el eje tenía una forma de aparecer. Los modelos de Gordon Broderick sugirieron problemas con el eje HPA podrían explicar el desequilibrio de género en ME.CFS, y el Dr. Bateman había propuesto que ME / CFS podría ser un trastorno inflamatorio centrado en el hipotálamo. Hace apenas un mes, un estudio sugirió que una interacción inmune-neuro-endocrina podría estar causando la fatiga en ME / CFS.

El principal hallazgo endocrino en EM / SFC fue cortisol bajo (hipocortisolismo). El hipocortisolismo también ocurre en el estrés crónico, donde el exceso inicial de cortisol se convierte en cortisol bajo a lo largo del tiempo y en el desarrollo de algo así como la sensibilidad al cortisol.

Pereira pensó que el eje HPA también podría explicar los problemas de desequilibrio de género. Las mujeres tienen más receptores de estrés que los hombres, y otra parte de la hipótesis (cubierta en el siguiente blog) encaja especialmente bien con las mujeres. Debido a que la respuesta al estrés tiene la intención de tomar el control y desviar recursos hacia / desde funciones críticas / no críticas, afecta la mayoría de los sistemas en el cuerpo. En general, Peireira pensó que los problemas del eje HPA podrían explicar la amplia gama de síntomas en EM / SFC.

Enfermedad a largo plazo: ¿tratamiento a corto plazo?

Sin embargo, aún existía el problema de los datos de seguridad animal a largo plazo. CT38 se había desarrollado inicialmente para uso a corto plazo y reunir datos de seguridad animal a largo plazo sería prohibitivamente costoso.

¿Cómo podría aplicarse un medicamento con datos de seguridad animal a corto plazo a una enfermedad crónica, a menudo de por vida, como ME / CFS?

Ahora viene la parte más intrigante y emocionante de la hipótesis de Pereira. Pereira no necesita datos de seguridad animal a largo plazo porque no planea hacer tratamientos a largo plazo. Si su hipótesis es correcta, él cree que CT38 podrá restablecer el sistema límbico casi tan rápido como se cayó de las vías en primer lugar; es decir, un par de tratamientos pueden ser suficientes para que el sistema vuelva a la normalidad y comience el proceso de curación.

Si la idea de una reversión más o menos instantánea después de décadas de enfermedad parece una especie de cuento de hadas, considere que Suzanne Vernon y Gordon Broderick propusieron algo similar hace unos diez años. Su modelo sugirió que un reinicio del eje HPA, al reducir drásticamente los niveles de cortisol durante un corto período de tiempo, podría provocar que el sistema se reinicie espontáneamente.

Esto no quiere decir que con el tiempo otros problemas médicos no hayan aparecido en algunos pacientes con EM / SFC que podrían complicar su situación. Eso es de esperar en cualquier enfermedad de décadas. Sin embargo, si Pereira y Cortene tienen razón, el núcleo de esta enfermedad podría ser susceptible de un cambio dramático.

La Parte 2 examinará la hipótesis de Cortene con mayor detalle y mostrará cómo intenta explicar los muchos síntomas y anomalías de ME / CFS. La Parte 3 explicará el enfoque del tratamiento y proporcionará detalles sobre el próximo ensayo clínico. (Health Rising no está afiliado con Cortene de ninguna manera).

En resumen: con la ayuda de un médico bien conocido dentro de la comunidad ME / CFS, Cortene llevará a cabo un pequeño ensayo de prueba de concepto en un único sitio en los EE. UU. Se seguirán los detalles, pero el diseño del ensayo tiene como objetivo obtener una evaluación rápida y objetiva de su fármaco y divulgarán los datos lo antes posible. Reiteran que esta es una investigación en fase inicial y que la precaución es apropiada.

[Klass]

Este es el primer post de tres. En cuanto traduzca el segundo, mucho más técnico, lo colgaré y luego resumo ambos.

Para la semana que viene Cort ya sacará el tercero que irá del estudio en humanos y el enfoque de tratamiento.