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Dr. Klimas compares GWI and ME/CFS, decries low ME/CFS funding

Ember

Senior Member
Messages
2,115

SMCI’s interview/presentation featuring Dr. Klimas provides a call to arms for fundraising advocates. NIH's funding inequity is highlighted in Jørgen Jelstad’s “The chronic lack of funds for ME/CFS research:"
For 25 years ME/CFS has been near the bottom of the list when it comes to funding for research. Perhaps Klimas refers to an exceptionally meagre year when she mentions the sum of $3 million, but in the larger perspective it is all the same. Over time the level of funding for ME/CFS research is deplorable.

The following graph shows NIH funding for ME/CFS research compared to three comparable diseases, MS, arthritis and lupus:

upload_2017-11-13_15-16-45.jpeg

These numbers say it all. NIH spends around $115 million on MS research every year. For ME/CFS, the number is $5 million. (Source: NIH Categorical Spending).

One single year of MS research equals about 23 years of ME/CFS research. That is just about all ME/CFS research ever done.

The same comparison with arthritis shows that one year of arthritis research translates into 50 years of ME/CFS research. And one year of NIH spending on HIV/AIDS is the equivalent of about 600 years’ worth of ME/CFS grants.
An NIH update with dollars in millions for the years 2013 to 2018 estimates low 2018 funding: MS--$77m; Arthritis--$193m ; Lupus--$76m; ME/CFS--$6m. Meanwhile, Dr. Klimas tells us:
About eight years ago, I had my first systems-biology data in ME/CFS. I was ready to start doing this modeling then. And you know, we’ve done a lot of work; it’s not that we’ve been idle. But we’ve done it, you know, smoke and mirrors and relatively small funds. But we are...in the ME/CFS world, we have the models. We know what to do. We are ready for human clinical trial. I should have been there, first. But there’s no place to go. It was so frustrating.... I dare say that this Gulf War trial that we’re just launching right now will be done in about a year” (2:00-2:30; 4:50-4:55).
“Eight years ago...but there’s no place to go.” Our advocates claim that, based on disease burden, NIH funding for ME/CFS research should be equivalent to $188 per patient per year:"
Why is funding so low?

Funding for ME/CFS is arguably the lowest per patient for any major disease in the United States, averaging to about $5 per patient per year. Compare this to multiple sclerosis, an illness with many similarities to ME, but which receives over $200 per patient per year.
How much should ME/CFS receive in funding per year?

While it may seem abhorrent in one way to quantify and compare suffering, it’s a necessity to determine whether or not the amount of funding allocated to ME/CFS research, treatment, and oversight is fair and reasonable.

The final DALY for ME patients was 0.714M or 714,000. In comparison to other illnesses, this projects that the funding for ME research should be equivalent to $188,000,000/year, or $188 per patient per year. That would be more than 25 times the funding allocated for research in the last calendar year in the US.
A 25-fold NIH funding increase is calculated by projecting an estimated ME/CFS Disability Adjusted Life Year (DALY) onto 2013 NIH data and using a modest prevalence estimate. It provides no compensation for past malfeasance.

Burden of disease is an important factor in NIH funding decisions, along with such factors as scientific opportunity, the quality of the science and the interest of researchers. But in the final analysis, a Washington Post article reports, less NIH funding may be provided to diseases “where we blame the victim” or there is less public support.
 

Ember

Senior Member
Messages
2,115
I’m amazed to learn that GWI has been reversed in mice and that a human trial is about to begin. As I understand it, neuroinflammation was first brought down by 50%, and then in quick succession, a dose of mifepristone was used to block the HPA axis, forcing an internal reboot. Bingo! The mice reset to normal. Their autonomic function normalized, their immune function normalized, their endocrine balance normalized and they could be normally challenged again. The mice had been “aged out” to the equivalent of ten years of illness (9:55–11:15).

It sounds as though an arm of the upcoming human trial might be devoted to ME/CFS (5:00–5:40), although I can’t imagine how that arm would get ethical approval without the prior modelling.

Could GWI be considered a form of cell danger response?
 

Diwi9

Administrator
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1,780
Location
USA
Something I learned from being on PR is that some months/years after falling ill, many people improve. I have improved this year. I can do more, but I still have a wall. I still have symptoms everyday, but they are not what they were when I was in bed. I do not understand this disease. I feel positive that it is neurological and immune mediated. It appears that GWI is not immune-related, but the consequence of a neurological insult.

It would not be surprising if some people deemed ME/CFS have had an exposure and are actually GWI-like. This research is amazing in that it may find a remedy for a fraction of us. The researchers are beginning to learn where to look to differentiate us.

We display the same clinical features, but we are not the same. This is profound. I'm surprised it is not receiving more attention.
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
Whoa... seems like they’re burying the lead here

At the end of the video Dr Klimas says a single dose of mifepristone cured GWI in their mouse model. What does that mean?

This study shows a negative overall outcome with mifepristone in human GWI subjects but with increased verbal learning
https://www.ncbi.nlm.nih.gov/m/pubmed/26600007/

Mifepristone is used to pharmacologically abort pregnancies and treat Cushing’s syndrome. More below
It is a steroidal antiprogestogen (IC50 = 0.025 nM for the PR), as well as an antiglucocorticoid(IC50 = 2.2 nM for the GR) and antiandrogen(IC50 = 10 nM for the AR) to a much lesser extent.[30] It antagonizes cortisol action competitively at the receptor level.[31]

In the presence of progesterone, mifepristone acts as a competitive progesterone receptor antagonist (in the absence of progesterone, mifepristone acts as a partial agonist). Mifepristone is a 19-nor steroid with a bulky p-(dimethylamino)phenyl substituent above the plane of the molecule at the 11β-position responsible for inducing or stabilizing an inactive receptor conformation and a hydrophobic 1-propynyl substituent below the plane of the molecule at the 17α-position that increases its progesterone receptor binding affinity.[32][33][34]

In addition to being an antiprogestogen, mifepristone is also an antiglucocorticoid and a weak antiandrogen. Mifepristone's relative binding affinity at the progesterone receptor is more than twice that of progesterone, its relative binding affinity at the glucocorticoid receptor is more than three times that of dexamethasone and more than ten times that of cortisol; its relative binding affinity at the androgen receptor is less than one-third that of testosterone. It does not bind to the estrogen receptor or the mineralocorticoid receptor.[35]
 

heapsreal

iherb 10% discount code OPA989,
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I’m amazed to learn that GWI has been reversed in mice and that a human trial is about to begin. As I understand it, neuroinflammation was first brought down by 50%, and then in quick succession, a dose of mifepristone was used to block the HPA axis, forcing an internal reboot. Bingo! The mice reset to normal. Their autonomic function normalized, their immune function normalized, their endocrine balance normalized and they could be normally challenged again. The mice had been “aged out” to the equivalent of ten years of illness (9:55–11:15).

It sounds as though an arm of the upcoming human trial might be devoted to ME/CFS (5:00–5:40), although I can’t imagine how that arm would get ethical approval without the prior modelling.

Could GWI be considered a form of cell danger response?

Mifepristone is that the drug they use for abortions as the day after pill? From memory it strongly blocks cortisol.

I wonder how they got neuroinflammation down and block cortisol as cortisol is probably our main hormones we have that reduces inflammation also??

Although going by what klimas said in that video cfs is the opposite with cortisol but still has neuroinflammation. I guess if we could naturally stimulate a normal cortisol level its possible this in itself could lower neuroinflammation but maybe need something else initially to help lower this inflammation. I wonder if just doing this is enough to improve nk function and put the many infections implicated into dormancy??
 

Ember

Senior Member
Messages
2,115
This study shows a negative overall outcome with mifepristone in human GWI subjects but with increased verbal learning https://www.ncbi.nlm.nih.gov/m/pubmed/26600007/
What cohort is being studied? The study that you cite is called "A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness (emphasis added).” Chronic multisymptom illness falls under the umbrella term, "medically unexplained illnesses," and it includes CFS and Fibromyalgia:
Gulf War Veterans’ Medically Unexplained Illnesses

A prominent condition affecting Gulf War Veterans is a cluster of medically unexplained chronic symptoms that can include fatigue, headaches, joint pain, indigestion, insomnia, dizziness, respiratory disorders, and memory problems.

VA refers to these illnesses as "chronic multisymptom illness" and "undiagnosed illnesses." We prefer not to use the term “Gulf War Syndrome” when referring to medically unexplained symptoms reported by Gulf War Veterans. Why? Because symptoms vary widely.

Military service connection

Gulf War Veterans who meet the criteria below do not need to prove a connection between their military service and illnesses in order to receive VA disability compensation.

VA presumes certain chronic, unexplained symptoms existing for 6 months or more are related to Gulf War service without regard to cause. These "presumptive" illnesses must have appeared during active duty in the Southwest Asia theater of military operations or by December 31, 2021, and be at least 10 percent disabling. These illnesses include:
  • Chronic Fatigue Syndrome, a condition of long-term and severe fatigue that is not relieved by rest and is not directly caused by other conditions.
  • Fibromyalgia, a condition characterized by widespread muscle pain. Other symptoms may include insomnia, morning stiffness, headache, and memory problems.
  • Functional gastrointestinal disorders, a group of conditions marked by chronic or recurrent symptoms related to any part of the gastrointestinal tract. Functional condition refers to an abnormal function of an organ, without a structural alteration in the tissues. Examples include irritable bowel syndrome (IBS), functional dyspepsia, and functional abdominal pain syndrome.
  • Undiagnosed illnesses with symptoms that may include but are not limited to: abnormal weight loss, fatigue, cardiovascular disease, muscle and joint pain, headache, menstrual disorders, neurological and psychological problems, skin conditions, respiratory disorders, and sleep disturbances.
VA acknowledges the IOM’s Gulf War and Health: Volume 10: Update of Health Effects of Serving in the Gulf War, 2016, which substitutes chronic multisymptom illness for Gulf War Illness:
In this tenth and final report in the series, an expert committee assembled by the IOM reviews, evaluates, and summarizes the available scientific and medical literature regarding health effects in the 1990-1991 Gulf War veterans, with special attention to neurological disorders (e.g., Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and migraines), cancer (especially brain cancer and lung cancer), and chronic multisymptom illness (Gulf War illness) (emphasis added).
The IOM's earlier Gulf War and Health: Treatment of Chronic Multisymptom Illness (2013) defines chronic multisymptom illness (CMI):
Chronic multisymptom illness (CMI) is a serious condition that imposes an enormous burden of suffering on our nation's veterans. Veterans who have CMI often have physical symptoms (such as fatigue, joint and muscle pain, and gastrointestinal symptoms) and cognitive symptoms (such as memory difficulties). For the purposes of this report, the committee defined CMI as the presence of a spectrum of chronic symptoms experienced for 6 months or longer in at least two of six categories—fatigue, mood, and cognition, musculoskeletal, gastrointestinal, respiratory, and neurologic—that may overlap with but are not fully captured by known syndromes (such as CFS, fibromyalgia, and IBS) or other diagnoses.
 
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Forbin

Senior Member
Messages
966
Her slide on "Climbing the Mountain" seems oddly reminiscent of the nature of quantum energy states, where there are discrete levels of stability but no "in between" states. A specific input or loss of energy is required to instantly shift between levels.

In GWI and ME/CFS it seems like the immune system may be switching into different levels/modes of stability based on an unusually strong response to something. The important thing being that, once it gets into that state, it will remain there even when the "trigger" is no longer present. It also doesn't seem like it would rely on a chronic infection to remain in this state. This really seems like another way of saying that the immune system is getting stuck in an alternate, but stable, mode.

It makes me wonder if the severity levels of ME/CFS are not just differences of degree but might be distinctly different stable states of the immune system.
 

Ember

Senior Member
Messages
2,115
It makes me wonder if the severity levels of ME/CFS are not just differences of degree but might be distinctly different stable states of the immune system.
Dr. Naviaux refers here to two distinctly different stable states: “The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem.”
 

Cinders66

Senior Member
Messages
494
This was a fantastic video, I thrilled GWS is progressing with better funding but it highlights even more the neglect of CFS. Although there's similarities it does seem some can improve either CFS whereas GWS seems more fixed but also I've not heard of the severe cases in GWS like in CFS , they seem more of the walking wounded or is that just because they weren't encouraged to exercise like PWME?

Nancy klimas presnting this at the SMCI discovery forum was exciting but I don't see how nih dont accept the bleeding obvious that if they pumped more money in CFS potentially thousands cost also be lifted out of disability with drugs. And I felt she was saying look what can be achieved. Phenomenal woman.

Finally the slide showing difference in communication on a slide was very interesting. It was a great video and there seemed real report with her and the excellent dr nahle.
 

Diwi9

Administrator
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1,780
Location
USA
@Cinders66 - From what I gathered, funding for GWI came from multiple government agencies (like DOD and VA). Right now, our only source is the NIH, and based on the interview with Dr. Koroschetz from the NIH (video thread link), it sounds like funding research grants happens via committee. Hence, it's a popularity game and the reason why some diseases are well-understood, while less popular diseases are under-funded/neglected. Dr. Klimas is amazing because as she does her GWI research, she's always considering what it can teach us about ME/CFS. I wish we had 30 of her in this field.
 

Mary

Moderator Resource
Messages
17,291
Location
Southern California
Whoa... seems like they’re burying the lead here

At the end of the video Dr Klimas says a single dose of mifepristone cured GWI in their mouse model. What does that mean?

This study shows a negative overall outcome with mifepristone in human GWI subjects but with increased verbal learning
https://www.ncbi.nlm.nih.gov/m/pubmed/26600007/

Mifepristone is used to pharmacologically abort pregnancies and treat Cushing’s syndrome. More below

I wonder if reducing neuroinflammation first by 50%, as Nancy Klimas said they did, and than adding in the mifepristone made the difference. I don't think they reduced neuroinflammation first by 50% in the study you cited.
 

Mary

Moderator Resource
Messages
17,291
Location
Southern California

SMCI’s interview/presentation featuring Dr. Klimas provides a call to arms for fundraising advocates. NIH's funding inequity is highlighted in Jørgen Jelstad’s “The chronic lack of funds for ME/CFS research:"

An NIH update with dollars in millions for the years 2013 to 2018 estimates low 2018 funding: MS--$77m; Arthritis--$193m ; Lupus--$76m; ME/CFS--$6m. Meanwhile, Dr. Klimas tells us:
“Eight years ago...but there’s no place to go.” Our advocates claim that, based on disease burden, NIH funding for ME/CFS research should be equivalent to $188 per patient per year:"
A 25-fold NIH funding increase is calculated by projecting an estimated ME/CFS Disability Adjusted Life Year (DALY) onto 2013 NIH data and using a modest prevalence estimate. It provides no compensation for past malfeasance.

Burden of disease is an important factor in NIH funding decisions, along with such factors as scientific opportunity, the quality of the science and the interest of researchers. But in the final analysis, a Washington Post article reports, less NIH funding may be provided to diseases “where we blame the victim” or there is less public support.

This is great, thanks so much for posting! :thumbsup:
 

Ember

Senior Member
Messages
2,115
Her slide on "Climbing the Mountain" seems oddly reminiscent of the nature of quantum energy states, where there are discrete levels of stability but no "in between" states....This really seems like another way of saying that the immune system is getting stuck in an alternate, but stable, mode.
Finally the slide showing difference in communication on a slide was very interesting.
The “Climbing the Mountain” slide, along with the graphic showing altered signalling pathways, suggests that a “snap out of it” remedy is being applied to a systemic “false illness belief.” Aren’t autoimmune diseases maintained by similar systemic "false illness beliefs?"
 

Ember

Senior Member
Messages
2,115
According to Dr. Naviaux, cellular miscommunication patterns maintain ME, GWI and some autoimmune diseases:
Prof. Naviaux suggests that autism, ME, the Gulf War Syndrome and some autoimmune diseases are caused by a disrupted interaction of the cells of the brain, intestine and the immune system, as well as by a dysfunction of the metabolism. For this reason, the question arises whether Suramin could possibly help with ME.
The systemic signalling errors described here do seem eerily analogous to “false illness beliefs,” i.e., danger responses in need of a reset. Meanwhile, we suffer the mistaken assessments of our systems.
 

Ember

Senior Member
Messages
2,115
From what I gathered, funding for GWI came from multiple government agencies (like DOD and VA). Right now, our only source is the NIH, and based on the interview with Dr. Koroschetz from the NIH (video thread link), it sounds like funding research grants happens via committee. Hence, it's a popularity game and the reason why some diseases are well-understood, while less popular diseases are under-funded/neglected.
Dr. Klimas frames the funding problem as one of portfolio management:
With the VA and the DOD, I mean DOD in particular, it’s a mechanism, congressionally directed medical research, phenomenal mechanism, because they can spin on a dime. They change the direction of what their portfolio is looking like every single year. They redo their whole thing. Okay, this is what we learned this year. What do we do with that knowledge that makes, in their focus...laser focus, ‘get these guys better’...move it to clinical trial? Move it; move it; move it. Fascinating stuff! But you know, we’re not doing hypothetical weirdness stuff here. We want stuff that’s going to help these vets. And I love that. It’s a really nice way to handle a portfolio (2:35-3:13).
The NIH, by contrast, provides no apparent mechanism for clinical trials: “So where are we in ME/CFS? You know, you’re looking at this thing and you’re saying: ‘Our NIH RFA is nice. It’s all about pathogenesis and what are the underpinnings. And yeah, you need to know that stuff to design clinical trials. But where is the mechanism to do a clinical trial (1:12-1:25)?’”

NIH portfolios receive little oversight, according to Dr. Koroshetz, and the system is risk adverse:
It’s pretty clear that the patients who are suffering from this illness are severely disabled, and they have a host of biological abnormalities, and so yes, this disease has a biological basis. The trouble is...we don’t actually know what is the unifying biology behind the disease. So in that sense, there’s a big mystery out there to be uncovered (6:00-6:25).
NIH is a granting agency, and the core of NIH is this very American process of jury by your peers. So the vast majority of NIH funds go to grants that come in and get reviewed and get a score that is highly meritorious. And then the institutes who have funds start paying the grants with the best scores until they run out of money. And that’s what we do in our institute. So the process is very much bottom-up and not very much top-down. We see very few [ME/CFS] applications. And that’s a problem. And that’s why got Dr. Collins to kind of pull the trigger on putting particular money not really to solve the...we don't think that this amount of money is going to solve the problem. We hope that this seven million, seven million a year for five years, so 35 million...but the key thing is that we think if we can start these consortia, that is seeding the research landscape, and the hope is that this will bring in more people from the centres and from outside the centres, and I’d say also...so there’s four centres in the program, but each of those centres is associated usually with four or five other hospitals or clinics. So it’s four times five times in terms of its breadth. But we definitely need people to come into this field to try and crack this mystery. This is not going to be easy. This is going to take real hard work, and a stroke of genius and a lot of luck, I think (12:10-14:07).
For me, ME/CFS is a really bad problem. But there are lots of really bad problems, and we need people working on them. And we don’t know where the discovery is going to come from. The discovery that solves ME/CFS could come from multiple sclerosis research. It could come from infectious disease research. So right now with ME/CFS, the difference with AIDS and ME/CFS is that AIDS identified the virus. Once we have our hands on what the inciting event is, then I think that will bring people to the field. In many fields that I’ve been in, when it’s not clear where you can kind of put your landing zone, where’s your beachhead from which to build your research out? As Zaher mentioned, a lot of people are not going to go into that field. They’re going to struggle, or they’re going to fail. It’s very high risk. So to get that beachhead to really understand something that we can really trust is central to the condition biologically--that I think will bring people in (18:35-19:45).
Dr. Koroshetz also notes, “The average grant is $443,000, so over five years, you’re talking close to two million dollars for every grant. So the taxpayer wants to make sure that at the end of that grant that you get something that’s solid. So that’s how the system goes (5:45-6:05).” From Dr. Koroshetz’ perspective, getting something that’s solid likely involves knowing the inciting event. And that’s bad news for ME/CFS, given Dr. Klimas’ disease model.

Big mysteries are apparently unpopular at the NIH. Far from providing clues to other diseases, our disease waits for discoveries from other portfolios to fall our way.
 

Ember

Senior Member
Messages
2,115
In GWI and ME/CFS it seems like the immune system may be switching into different levels/modes of stability based on an unusually strong response to something. The important thing being that, once it gets into that state, it will remain there even when the "trigger" is no longer present. It also doesn't seem like it would rely on a chronic infection to remain in this state. This really seems like another way of saying that the immune system is getting stuck in an alternate, but stable, mode.
Back in 2013, Dr. Broderick described alternate resting states found in males suffering from GWI and CFS. He presented pilot data suggesting that, as a persistent state, CFS is quite far removed from the ones that occur naturally. “You would need an external force to keep you at that attractor” (25:50 – 29:00). By contrast, GWI in males “sort of hangs around or orbits a normal resting state...”
consistent with the model that they’ve been exposed to a toxin, and they’ve been removed from the battlefield after that, so that the toxin or the insult is not persistent here, yet they’re still sick. So part of the body’s normal homeostatic drive or regulatory drive has now taken over and might be in cahoots with the insult or might be in a permanent or chronic reaction to that insult.