Dr. Cheney comments on the XMRV workshop

[Kate_UK]

Wasnt there someone currently doing this on caviers? (ohh not sure if i have the word right.. on dead ME peoples bodies)

Maybe Ila Singh?

 

[Kate_UK]

The pulmonary alveolar macrophages were absolutely loaded with XMRV virus ............ It would seem that bronchial secretions.......are well positioned to help the virus to spread itself to other macaques, especially if activated.

I think I remember something. From one of Byron Hyde's talks at one of the Invest in ME conferences, I think he said that a really high risk job for getting ME was to be a pulmonary technician. He spoke at the 2006 and 2007 conferences, but I only have the 2006 DVD to check - does anyone have the 2007 one?

 

[pamb]

Just chiming in with anecdotal evidence supporting the three strikes theory:

My husband is the CCC person in our family and we have learned through the thousands spent in the alternative treatment world:

1. He has a genetic issue that means he clears toxins less quickly than most do. (sorry I don't have the proper name - it's in stacks of files)
2. He does have a pretty high pesticide load.
3. We both caught a nasty flu in December 2000. I was in bed for about 3 days, and recovered as normal, despite a huge amount of stress in my life. He has never recovered.

hmmmmm. Now, as winter approaches, I'm really wondering if we need to sell our house (probably at a loss) and move to a dryer climate. We are in the Dordogne region of France. Hot summers and short winters, but above freezing and very damp. His winters here have been pretty bad, but we had blamed it on being housebound. Maybe it is more damp related? Thank heavens we keep the dehumidifier running all year. Maybe I'll buy another one for the bedroom as we just have a portable unit that lives in the bathroom or laundry room.

 

[Julia Rachel]

Incredibly Insightful and well worded for understanding. The cervix connection intrigues me greatly. So many women opt to leave their ovaries in as well as the cervix when doing a hysterectomy, CFIDS patients now may rethink this philosophy with future incoming information. My son has CFIDS, which began at Puberty. My cousin has Chrohns and is believed to have undiagnosed CFS. Another cousin has full blown CFIDS and Fibro. My Grandmother passed away of a very rare type of Sinus Cancer. My biological father had Prostate Cancer. I am beginning to connect all the dots.....especially when I've learned in speaking with MANY other patients with CFIDS who have experienced GYN, GI Tract, Stomach Issues as well as enlarged Spleens and Liver Issues. Interesting that the new study at Stanford includes Borrelia in its' XMRV study with Columbia University. Thank You Rich and Dr. Cheney!!!

 

[SA2]

I think that CFS symptoms might be caused by a damaged immune system and not by XMRV directly for several reasons: 1) ~5% of all individuals have XMRV but only ~0.5% have CFS symptoms which means 90% of the people with an XMRV infection do not have CFS symptoms, which means XMRV by itself does not seem to cause CFS symptoms. 2) Ampligen is one of the most effective drugs for treating CFS and works by stimulating the anti-viral pathway in the immune system, which appears to be damaged in people that have CFS symptoms. 3) CFS has been well characterized as following a variety of initial infections (EBV, HHV6, Q Fever, enteroviruses, etc, see http://www.youtube.com/watch?v=oOcDfd5sA1k&NR=1 for instance).

By the way, the genetic component of CFS might be XMRV, since XMRV can be inherited. In this scenario, XMRV being a retro-virus, is transmitted (perhaps primarily) via inheritance (perhaps in 4-7 % of the population), does not cause any outward symptoms until some trigger agent (EBV, HHV6, etc) in combination with XMRV damages the immune system which then causes CFS. The 90% majority of people carrying XMRV (the 90% above) never get CFS triggered but can transmit the genetic component (XMRV in this scenario) to some of their children via inheritance.

The outbreaks of CFS could be caused by an outbreak of the trigger agent in the community.

Notice that in the above scenarios, anti-retrovirals may not help to relief CFS symptoms since the symptoms are primarily caused by a damaged immune system which causes heavy cytokine production, and XMRV acts as an initiator rather than a sustainer of the illness symptoms.

 

[SA2]

On the other hand, in the above scenario, XMRV may not only be an initiator but also a sustainer of the symptoms, by continually renewing the damage to the immune system and also by increasing the production of cytokines itself after the immune system has been damaged. In this scenario, anti-retrovirals could provide some symptom relief.

 

[slayadragon]

Can you in a paragraph or two, making it simple.. explain why this it is thought that mold is more problematic then other toxins or reactions we may get to things??

It's seeming that it's time to start separating out the factors that might make us more likely to get ME/CFS (or to stay really sick with it) from those factors that seem like they are MUCH more likely to make that happen.

For instance, as Erik wrote, "In 1985, when I told Dr. Cheney about this weird effect, he said CFS was viral. I just replied that for some reason, mold had a specificity to it that made it worthy of investigation. That specificity is the reactivation of latent infections of almost any sort." (2007)

And also: "This one mold reactivity stood out as a specificity. I just concentrated on it - and much to my amazement, the other sensitivities just faded away." (2006)

If mold reactivates XMRV while other toxins do not, and if the reactivation of XMRV is the cause of the sensitivities to other toxins, then this is making a whole lot of sense.

Several of us have noticed that if we just avoid mold, all our reactivities to everything else - pesticides, air fresheners, gasoline, various foods, perfume, EMF's - fade away. Avoiding all those things (though granted I never tried "extreme pesticide avoidance") never helped make ANY of the other sensitivities diminish at all.

We know that (per Mikovits) the factors that cause XMRV to (re-) activate are: cortisol, inflammation, androgens and estrogens. Things that debilitate the immune system also would seem likely to contribute to that happening. And as Rich suggests, oxidative stress seems to be an issue too.

It seems to me that the specificity of mold (meaning trichothecenes) is that it fits into this paradigm really well. It exercises its toxicity almost solely through inflammation and oxidative stress; the systems of people exposed to it become cortisol-heavy; and it has big effects on the immune system.

Most toxins don't do any of those things.

(Another couple of relevant things the trichothecenes do especially well: make holes in the blood-brain barrier, cause intestinal permeability, and "eat up" reduced glutathione.)

So I think that when we're looking for other "primary" suspects that are at the core of ME/CFS, we should be considering how well they fit these factors.

Two chemicals that fit that description really well are phosphine and naphthalene. I did an experiment this past winter where I deliberately exposed myself to a touch of phosphine (by dissolving some rat poison pellets in vinegar), and it did give me the same "response" as the mold. (If this sounds stupid, please note that I regularly am affected more by the mold/cyanobacteria I encounter inadvertently on a daily basis.) Another person reports that naphthalene (a chemical present in old-fashioned mothballs) had similar effects to mold (for for him, more intense) as well.

Vaccines appear to have some of these characteristics, Cheney suggests. I need to find out more about how they work.

Certain infections (Lyme, colds/flus and - I think we will find - candida) seem to have the potential of doing this.

Interestingly, gluten seems to have the inflammatory and oxidative stress characteristics. Two days ago, I interviewed an Incline Village epidemic survivor who has mostly recovered as a result of extreme gluten avoidance, along with antivirals/antibiotics/detox. She knows that mold is a part of her history and says she's in a good residence now, but the gluten is key for her.

So there's a good starter list of substances that we might think of as CORE problems for us.

Do EMF's fit into this category, based on what we know of their mechanisms?

What other substances or stressors seems to be PARTICULARLY good candidates for placement on our list?

Thanks, Lisa

 

[Francelle]

Rich, Sorry if I've missed this somewhere else but wasn't Cheney meant to have a poster presented at the conference?

 

[anciendaze]

Rich, Sorry if I've missed this somewhere else but wasn't Cheney meant to have a poster presented at the conference?

He did Francelle, but poster sessions are not part of the official program. They basically consist of the presenter standing next to a poster about findings, where anyone interested can ask questions.

 

[KnightofZERO]

Saliva Test?

The only test that looked at respiratory secretions, the German Article from a few months ago (in healthy and immunodeficient) had no problem finding XMRV, and if they had known about the heterogeneity in the DNA sequence at that time, it would have presumably been even easier for them.

I wonder, even if these virologists are fixated on a blood test, using serology/nucleic acids (seemed like it a lot from the conference), if it might not still be useful to develop means for quantifying the amount of virus in respiratory secretions... it doesn't seem too difficult, and this is one piece of strong circumstantial evidence that the infection level may be highest there.

Also if that information from macaques is consistent to humans it seems like looking for antibodies to XMRV/MLV is of, at best, limited value.

 

[ixchelkali]

Heres my attempt to summarize the macaque study part in vastly over-simplified terms:

They injected the monkeys with XMRV. Within a few weeks the XMRV was largely gone from the blood. After a while, even the antibody response to the virus went away, apparently because there wasnt enough virus residue to stimulate an antibody response.

However (and this is where it gets interesting), they found the virus hanging out in organs all over the body. Retroviruses use a key called a receptor to gain access to cells. The receptor that XMRV uses, called Xpr1, is found in many different tissues of the body (e.g., spleen, lymph node, thymus, leukocytes, bone marrow, heart, kidney, pancreas and skeletal muscle). They found the virus concentrated in lymphoid organs (that is, ones involved with the immune system, like the spleen and gut lining) and in the sex organs.

One kind of cell that seems to act as a reservoir for XMRV are called tissue macrophages, which are immune cells, mature white blood cells that have left the bloodstream and now live in tissue. They found a lot of XMRV in these cells in the lungs, so Dr Cheney thinks that bronchial secretions, as well as other bodily secretions, could help spread the disease, especially when the virus is active.

Okay, so how does a low-level inactive virus become active? The virus reacts to both glucocorticoids and to androgens. Androgens are sex hormones. Glucocorticoids are the part of the immune system that tell it to shut down when its activated (they also react to cortisol and help metabolize sugars, and other processes). So the virus could be activated in tissue where youd find sex hormones, like the prostate. It could also be activated by severe stress, allergies, or when the immune system is fighting a pathogen.

In macaques where XMRV had apparently been completely cleared from the blood, when they injected them with a bunch of peptides (short proteins that would act as an allergen or foreign particle to activate the immune system), there was a big reactivation of the virus. This suggests that once youre infected, even though the virus is gone from the bloodstream, it may lie low in tissues and different kinds of stimulus could trigger a reactivation.

 

[free at last]

Hi, illsince1977.

He actually wrote that the virus was cleared from the blood, not from the blood and tissues. So the idea is that there are reservoirs in the tissues, though it may be hard to find signs of the virus in the blood. The peptides caused the virus that was in the tissue reservoirs to flare, and then they could be found in the blood again.

I think that's the essence of it.

Rich

the best way to look for xmrv in the blood is to reactivate it, though the extra symptoms that could rise, might put a lot off this idea

 

[slayadragon]

Here’s my attempt to summarize the macaque study part in vastly over-simplified terms:

They injected the monkeys with XMRV. Within a few weeks the XMRV was largely gone from the blood. After a while, even the antibody response to the virus went away, apparently because there wasn’t enough virus residue to stimulate an antibody response.

However (and this is where it gets interesting), they found the virus hanging out in organs all over the body. Retroviruses use a “key” called a receptor to gain access to cells. The receptor that XMRV uses, called Xpr1, is found in many different tissues of the body (e.g., spleen, lymph node, thymus, leukocytes, bone marrow, heart, kidney, pancreas and skeletal muscle). They found the virus concentrated in lymphoid organs (that is, ones involved with the immune system, like the spleen and gut lining) and in the sex organs.

One kind of cell that seems to act as a reservoir for XMRV are called tissue macrophages, which are immune cells, mature white blood cells that have left the bloodstream and now live in tissue. They found a lot of XMRV in these cells in the lungs, so Dr Cheney thinks that bronchial secretions, as well as other bodily secretions, could help spread the disease, especially when the virus is active.

Okay, so how does a low-level inactive virus become active? The virus reacts to both glucocorticoids and to androgens. Androgens are sex hormones. Glucocorticoids are the part of the immune system that tell it to shut down when it’s activated (they also react to cortisol and help metabolize sugars, and other processes). So the virus could be activated in tissue where you’d find sex hormones, like the prostate. It could also be activated by severe stress, allergies, or when the immune system is fighting a pathogen.

In macaques where XMRV had apparently been completely cleared from the blood, when they injected them with a bunch of peptides (short proteins that would act as an allergen or foreign particle to activate the immune system), there was a big reactivation of the virus. This suggests that once you’re infected, even though the virus is gone from the bloodstream, it may lie low in tissues and different kinds of stimulus could trigger a reactivation.

Stachy seems to be pretty good at screwing up the immune system, and a lot of its activity seems to be by causing inflammation and toxicity to the macrophages.

I put some research abstracts about this on this thread:

http://www.forums.aboutmecfs.org/sh...ic-Mold-Research-Articles&p=122156#post122156

So I would think that macrophages that are screwed up would be more likely to host XMRV virus.

Which....oh! now I have a theory for why detoxification helps people to get better.

Maybe the toxins stored in the body exert perpetual pressure/damage on the macrophages, allowing the viruses to get lodged in there.

This is Amy Yasko's theory, actually. That the toxins and the viruses cling together in what I envision as a sort of goo (probably that's not literally correct), and that in order to prepare to get rid of the viruses (she suggests Valtrex) detoxification should be done first.

That's how I pursued it too. 18 months of detoxification, then Valcyte/Famvir.

A little bit slow, this route. It would be nice if somebody came up with something quicker.

But I think that you'd still need to do detox, if you really wanted to clean out the reservoirs.

And you'd still need to not live in moldy buildings and be careful with not piling too many of those specific stressors on top of one another, if you wanted to stay well once you got there.

Best, Lisa

 

[usedtobeperkytina]

I think that CFS symptoms might be caused by a damaged immune system and not by XMRV directly for several reasons: 1) ~5% of all individuals have XMRV but only ~0.5% have CFS symptoms which means 90% of the people with an XMRV infection do not have CFS symptoms, which means XMRV by itself does not seem to cause CFS symptoms. 2) Ampligen is one of the most effective drugs for treating CFS and works by stimulating the anti-viral pathway in the immune system, which appears to be damaged in people that have CFS symptoms. 3) CFS has been well characterized as following a variety of initial infections (EBV, HHV6, Q Fever, enteroviruses, etc, see http://www.youtube.com/watch?v=oOcDfd5sA1k&NR=1 for instance).

By the way, the genetic component of CFS might be XMRV, since XMRV can be inherited. In this scenario, XMRV being a retro-virus, is transmitted (perhaps primarily) via inheritance (perhaps in 4-7 % of the population), does not cause any outward symptoms until some trigger agent (EBV, HHV6, etc) in combination with XMRV damages the immune system which then causes CFS. The 90% majority of people carrying XMRV (the 90% above) never get CFS triggered but can transmit the genetic component (XMRV in this scenario) to some of their children via inheritance.

The outbreaks of CFS could be caused by an outbreak of the trigger agent in the community.

Notice that in the above scenarios, anti-retrovirals may not help to relief CFS symptoms since the symptoms are primarily caused by a damaged immune system which causes heavy cytokine production, and XMRV acts as an initiator rather than a sustainer of the illness symptoms.

This is my theory but I draw another conclusion. And it follows the HIV model.

Mikovits showed how there is androgen and / or cortisol or immune system activation which increases level of virus. And at some point, it tips the scale where the body's immune system is too damaged to get the virus and other reactivated infections under control. So, the body keeps trying to fight it by sending out cytokines, which makes us feel sick. But as soon as immune system starts winning the battle, we go do stuff which causes cortisol or we have a hormone spike which causes virus to replicate again. I think this would explain why there is an association with other viruses, such as mono and why we tend to gradually see some improvement, but can relapse at another assault. This would explain why middle-aged women are highest demographics to get CFS, with teenagers of both sexes next.

I have begun to think of our illness as being like a Vietnam War of our immune system and the causal agent constantly fighting in a see - saw fashion, taking turns getting the upper hand. But neither completely winning. So there must be something that is feeding the causal agent, which is why androgens, cortisol and immune system activation makes sense.

But, good news is that our body makes new immune system cells from the bone marrow. So I see hope if you can lessen the activators, hinder the virus replication and boost the immune system, then we may have it in our tissue, but we won't have "CFS".

Also, I do think this is another voice saying the best analogy for this virus is Felv. Wonderful that such an expert was included.

Also, clearly, this virus must hide or else it would have been found years earlier. It is unique in many ways. And that tells me there are likely many other viruses that have similar behavior and have not yet been discovered.

Tina

 

[illsince1977]

Hi, illsince1977.

He actually wrote that the virus was cleared from the blood, not from the blood and tissues. So the idea is that there are reservoirs in the tissues, though it may be hard to find signs of the virus in the blood. The peptides caused the virus that was in the tissue reservoirs to flare, and then they could be found in the blood again.

I think that's the essence of it.

Rich

I re-read it and it says "Over time, the infections of various organs tended to be cleared."

That was where I got it! But upon my 2nd and 3rd reading I finally saw the part about macrophages acting as reservoirs, so now I understand the reservoir part of my question.

However, I'm still reading that it was cleared from the tissues. Did I still misunderstand, Rich?

 

[illsince1977]

Heres my attempt to summarize the macaque study part in vastly over-simplified terms:

However (and this is where it gets interesting), they found the virus hanging out in organs all over the body. Retroviruses use a key called a receptor to gain access to cells. The receptor that XMRV uses, called Xpr1, is found in many different tissues of the body (e.g., spleen, lymph node, thymus, leukocytes, bone marrow, heart, kidney, pancreas and skeletal muscle). They found the virus concentrated in lymphoid organs (that is, ones involved with the immune system, like the spleen and gut lining) and in the sex organs.

[/SIZE]

And they told us we were imagining things because nothing could possibly cause such multisystemic symptoms except our overactive imaginations. Funny how all of us wound up with an such a similar set of imagined symptoms.
:victory:

Good job on the summary Ix!

 

[alex3619]

Hi

I would like to make two general points. First, a restriction enzyme typically targets viral RNA or DNA. The science of genetic engineering is based on this because they can be used to cut DNA at specific points.

The second things is that we don't want to do this to attack XMRV DNA. It will help to cut XMRV RNA in two, stopping the virus dead, so would be a useful drug in this sense, but we want to mutate or inactivate the viral DNA in our own genome. This would require a very specific drug, possibly something containing a long sequence of human-like RNA or DNA. I think it can be done, but it will take years of research. If we can develop such a drug, it will turn XMRV DNA in our genome into junk DNA, ending its chance of reinfecting us.

Bye
Alex

PS Maybe this can be called the Junk XMRV solution?

 

[Bob]

... I have to say that the presentations of XMRV association with CFS (4 presentations) were much stronger than the presentations of negative XMRV associations with CFS (4 presentations). They were stronger specifically because of the multiple methods they employed and not just PCR. Very interesting in this regard were comments by the head of the blood working group at the NIH who is trying to determine the cause of the discrepancy. He hinted strongly that it is the way blood is collected and processed for nucleic acids and not the detection methods for XMRV itself that divides the two groups. In an NIH blood group sponsored study, a group comparison study with both camps represented detect successfully, in a blinded fashion, XMRV spiked buffer in varying concentrations but they nevertheless divide into two camps when clinical blood samples are taken and processed for XMRV nucleic acids. Using only PCR, one camp sees ~80% positive in CFS and one camp sees 0% positive in CFS There is no one in between and no middle ground between the two groups which was striking and noted by Joe B. who was also in attendance. There is no evidence by mouse mitochondrial DNA probes, that any of the positive associations were contaminated.

I found this paragraph very promising and hopeful...
For me personally, it explains the reason for the zero/zero studies, and I'm very pleased that the blood working group is working this out and seeing the zero/zero studies for what they are...
The head of the blood working group seems to be specifically saying that the zero/zero studies are probably related to the way the blood samples are collected and processed because, in their own studies, one group is detecting the virus at 80% (using PCR only) whereas another group is testing the same blood, but using different methodology, and is detecting the virus at zero percent.
This flushes out the inadequacies of the methodology of all the zero/zero studies, and explains the reasons for the zero/zero detection rates.

Of course, we've still got to be vigilant about the CDC's 'mock-ME' patient samples and I think we've got to create an almighty storm if they are used again in any research.

 

[Sasha]

Here’s my attempt to summarize the macaque study part in vastly over-simplified terms...

Thanks, ix - that was just what I needed!

 

[Rrrr]

This is my theory but I draw another conclusion. And it follows the HIV model.

Mikovits showed how there is androgen and / or cortisol or immune system activation which increases level of virus. And at some point, it tips the scale where the body's immune system is too damaged to get the virus and other reactivated infections under control. So, the body keeps trying to fight it by sending out cytokines, which makes us feel sick. But as soon as immune system starts winning the battle, we go do stuff which causes cortisol or we have a hormone spike which causes virus to replicate again. I think this would explain why there is an association with other viruses, such as mono and why we tend to gradually see some improvement, but can relapse at another assault. This would explain why middle-aged women are highest demographics to get CFS, with teenagers of both sexes next.

I have begun to think of our illness as being like a Vietnam War of our immune system and the causal agent constantly fighting in a see - saw fashion, taking turns getting the upper hand. But neither completely winning. So there must be something that is feeding the causal agent, which is why androgens, cortisol and immune system activation makes sense.

But, good news is that our body makes new immune system cells from the bone marrow. So I see hope if you can lessen the activators, hinder the virus replication and boost the immune system, then we may have it in our tissue, but we won't have "CFS".

Also, I do think this is another voice saying the best analogy for this virus is Felv. Wonderful that such an expert was included.

Also, clearly, this virus must hide or else it would have been found years earlier. It is unique in many ways. And that tells me there are likely many other viruses that have similar behavior and have not yet been discovered.

Tina

very helpful post!