XMRV and Culturing, HERV's and more

[dannybex]

I agree...

I very much appreciate Kurt laying out in detail his ideas about XMRV and HERV's - I learned quite a bit.

The transmission question has never fully been addressed and it is an important one. Its funny how some aspects of this just go by the wayside. Anyway if XMRV is a blood borne retrovirus then I think Kurt is saying we should see regular passage from the mother to her children and between sexual partners. While we see both (Mother/children and sexual partners with CFS) both are pretty rare. This would seem to argue against an obvious viral cause of CFS.

Instead Kurt, if I got it right, lays out a theory of another breakdown in the body - first high rates of oxidative stress wiping out glutathione (Pall + VanKonynenburg?) which then results in herpesvirus activation.

The fact that the epidemiology of CFS does not - except for those outbreaks - appear to look viral - suggests that other elements must come into play. The viral trigger is certainly there, we know that - but CFS appears to be triggered by a variety of viruses (with EBV at the top of the list) as well as other stressors as well as sometimes nothing - so there's no really clear single factor. The Dubbo studies showed us that; four pathogens, if I remember correctly -which all caused CFS. This suggests that the problem has to be deeper - in something that happens in relation to the infection.

I wonder if you can fold the Dubbo projects finding of high pro-inflammatory cytokine levels in people who went on to get CFS (versus low cytokine levels in people who did not) in this scenario. In that scenario you have an infection (a stressor), high cytokine levels - then what? high rates of oxidative stress... That fits in well with Kurts scenario.

I agree in general re the multifactorial model, but what's often left out of the equation in discussions about XMRV (and CFS/ME in general) are other potential triggers, or IMHO probably multiple triggers that overwhelm the immune system, or cause it's dysfunction -- besides viral or bacterial infections. Or I should say perhaps...in addition to viral or bacterial infections.

I hate to sound like a broken record, but many patients have found that mold was a huge issue (like Erik Johnson, from the Tahoe outbreak), or mercury and/or other heavy metals, not to mention pesticides and other chemical (environmental) exposures. All of these things may deplete glutathione, disrupt liver function/methylation, mess up gut function, and/or screw up immune function. Perhaps Rich could comment on this...?

I also totally agree that it would be WONDERFUL if there was (or maybe IS) 'one' cause for CFS/ME. But I worry that some people may be putting all their eggs in one basket, and if...IF...XMRV doesn't turn out to be 'the' underlying cause, then...what will happen if you've pinned all your hopes on it?

Just from my own experience, and from reading about other's stories, and from meeting people in my local area who I knew when they were very ill and have actually recovered (rare, but it does happen), or are recovering...I see a pattern: all had or have different triggers, different rates of onset, different areas of the body that are affected or not, and thus will need different tests and treatments to address those issues.

I'll end by quoting Judy Mikovits, when asked a question about gradual onset cases:

"Question: Is there differences between – because you’ve got a big population of patients with sudden onset and then you’ve got a big population that had gradual onset. And a lot of the gradual onset patients are worried that “Maybe I don’t fit this equation.” So what would you say to that?

Judy: That little bump is smaller, so it’s not a huge burst. So that it was little insults over time. I think, for me anyway, I know only a handful that I’ve looked at, that I know the patients and I know what the onset was. But the gradual onset there’s no real difference between – it just depends on that environment, what the other triggers and events were that spurred it on. So I don’t see if you are gradual onset, it doesn’t mean that you might not be infected as well."

okay, I'll shut up. :Retro smile:

d-bex


p.s. Thanks too, to Kurt, Cort, and Gerwyn and all for this discussion.

 

[Robin]

I very much appreciate Kurt laying out in detail his ideas about XMRV and HERV's - I learned quite a bit.

The transmission question has never fully been addressed and it is an important one. Its funny how some aspects of this just go by the wayside. Anyway if XMRV is a blood borne retrovirus then I think Kurt is saying we should see regular passage from the mother to her children and between sexual partners. While we see both (Mother/children and sexual partners with CFS) both are pretty rare. This would seem to argue against an obvious viral cause of CFS.

Why? Does the progression from XMRV to CFS have to be like HIV to AIDS? Maybe a large number of people never progress or some just take years, maybe 20 or 30 and haven't gotten it yet... Until we have a reliable test, we won't know anything about family or sexual cohorts.

Also, there are viruses that are largely asymptomatic in most people (95% do not have symptoms, less than 1% cause paralysis). We don't know anything about XMRV, or enough to conclude much, at all, about transmission.

I think concluding that CFS can't be viral or retroviral by the present epidemiology is premature.

 

[_Kim_]

But I worry that some people may be putting all their eggs in one basket, and if...IF...XMRV doesn't turn out to be 'the' underlying cause, then...what will happen if you've pinned all your hopes on it?

Nothing happens. People experience disappointment. They get over it.

You have not - in my opinion - been trying to pour cold water on people's hopes, but simply to issue a warning that if our hopes rise too high, they risk crashing hard, taking countless patients with them.

I disagree. It seems to me that all Kurt does is try to pour cold water on people's hopes. His message does not come across as caring warnings about our well being.

If ME/CFS patients are nothing else, they are resilient. We'll weather our disappointment if XMRV does not pan out. We are not that fragile that we need others to squelch our hope just for caution's sake.

... maybe I should just leave people here to build up hopes they want to have.

Good idea!

 

[Jody]

I for one am very interested in hearing what Kurt has to say.

 

[Jody]

Let's keep the discussion on topic, Kim, rather than criticizing other posters.

 

[dannybex]

Nothing happens. People experience disappointment. They get over it.

Tell that to Sue for one. She's extremely distraught and desperate over this issue. My goodness Kim, perhaps you can 'get over it' easily, but it's awfully presumptuous to presume everyone else, especially those who are severely ill, can do the same.

I disagree. It seems to me that all Kurt does is try to pour cold water on people's hopes. His message does not come across as caring warnings about our well being.

Then you haven't been reading his entire posts, nor those of others. We'll have to agree to disagree. I for one appreciate his caution, and that of several others that have had the courage to bring up concerns.

If ME/CFS patients are nothing else, they are resilient. We'll weather our disappointment if XMRV does not pan out. We are not that fragile that we need others to squelch our hope just for caution's sake.

Yes, we're resilient, but some more than others. Some are definitely very, very fragile...clinging to any hope out there. I know several people who have suggested that if this doesn't pan out, they may just give up.

 

[dannybex]

I for one am very interested in hearing what Kurt has to say.

As am I, and I have no doubt that others feel the same way.

 

[Kati]

I concur with Kim.

I think that science aside, it is important to for people to hold on to hope. Please let me live in my bubble until the second positive replication study (after the Japanese one that is). Please let me believe that Dr Judy has done an astounding job with her science and surrounded by very very bright people that worked together to get this result.

Publishing in Science is not a small thing. One has to give credit for this achievement. This woman is Nobel Prize potential. For one of the rare times in the history of ME/CFS, someone decided to take a chance and look for a cause, and a treatment. We owe that to Mr and Mrs Whittemore, and for Dr Judy to leave her job as a bartender and move out in the mountains to search for a retrovirus. That woman has guts! And I love it.

 

[Lily]

Well, I do read what Kurt has to say, since I do like to hear all sides. I just read it, ignore the arrogance and and bite my tongue. It really is about tone (or perceived tone, since this is the internet). I even considered PMing him to tell him about the tone, but decided that he likes the tone. Nobody is perfect. Ya just have to overlook some things.

 

[Jody]

Lily, we're trying to stay on the topic. It isn't Kurt and his "tone".

 

[gracenote]

I just wonder why XMRV has captured the attention of some of our top CFS doctors Peterson, Cheney, Klimas, Bell if they didn't think there was something to it. For some reason they have thought it might be a fit with CFS and, as of now, have not publicly stated otherwise.

It is my understanding that the transmission issue has been addressed, and so has the idea of outbreaks. See the Cheney / Mikovits transcript.

I do realize that there is much we don't yet know, but we do know that some of our most respected CFS doctors are taking XMRV seriously. I don't think it is inappropriate for us to hold out a bit of hope while we wait for more information. Meanwhile, I'll read what everyone has to say, pretend I understand a bit of the science (I wish), and keep doing what I'm doing to manage as best I can.

But I sure liked the "game changer" headlines better than the "muddy waters" ones. Cort, I can't wait for you to have some fabulous news to write about.

 

[Cort]

It so hard to know what to think. Honestly I go so up and down with this - I'm confident one day and dashed the next. There are times I think it can't fail and times I've sworn to myself that its all over. I've never been around something so topsy turvy. I think everyone - from Dr. Klimas to Dr. Cheney to whomever has been surprised by the results so far.

Something just showed me an email from Dr. Mikovits- who's basically counselling her through a rough spot. I must say she is an extremely giving and compassionate person - it's quite remarkable really.

Anyway in her letter she says the staff at WPI is run ragged and the NIH researchers are yelling at each other because this is moving so slowly and then she ends it by saying 'we are learning so much about this infection!'.

Anyway I should have a nice blog about a new team joining the hunt for XMRV in CFS.

For me Kurt is an anchor. He looks at things very objectively and I appreciate that VERY much. I like the technical expertise he brings - I like that kind of stuff. I don't see arrogance - I see someone who's willing to step mostly alone into a very difficult situation - that's not easy - and who has been provoked quite a few times and has remained quite calm.

This has all left us a bit ragged. Its left me edgy thats for sure.

I think April is going to be a very interesting month. Lets just hang in there!

 

[julius]

I can't imagine a situation where having an open mind is a bad thing. To believe in something is one thing, but to have a closed mind is completely another. I remember making a similar (or exact) post in the faith healing thread. I don't know if anyone agreed with what I said, but I still stand by it.

Everyone knows the saying of how a great chess player thinks so many moves ahead. He is planning for all eventualities. He is prepared. But that does not mean he has no confidence in his current move. He might have great conviction in it, but he must have an open mind to several different possible outcomes.

I think XMRV is it! I HOPE XMRV is it! But if it isn't, what benefit will it have been to have kept our heads buried in the sand. None.

What benefit could there be to having a theoretical discussion right now? Well, possible new ideas and approaches in the event that things should turn out poorly for our dear XMRV.

I understand that for some it brings them down, and they feel like someone is putting a turd in the punchbowl. Unfortunately life sometimes gives you turds.

 

[dannybex]

Excellent points Julius...very well put.

 

[natasa778]

it is my understanding that the transmission issue has been addressed, and so has the idea of outbreaks. See the Cheney / Mikovits transcript.

So have all other points Kurt that you keep bringing up, contamination has been addressed (why not controls etc, also Science was all over them for this one, making sure it wasn't there...) , HERVs have been addressed (sequences non matching), transmission, antibodies.... Whenever something is addressed you go back a step - antibodies one example. Read Judy's comments on why those antibodies in Science were still valuable, and take it from there, don't go back to the old statement without taking new things on board. Btw they never ever presented them to be what they are not, VIP only talking about specific ones being developed...

 

[Lily]

I can't imagine a situation where having an open mind is a bad thing. To believe in something is one thing, but to have a closed mind is completely another. I remember making a similar (or exact) post in the faith healing thread. I don't know if anyone agreed with what I said, but I still stand by it.

Everyone knows the saying of how a great chess player thinks so many moves ahead. He is planning for all eventualities. He is prepared. But that does not mean he has no confidence in his current move. He might have great conviction in it, but he must have an open mind to several different possible outcomes.

I think XMRV is it! I HOPE XMRV is it! But if it isn't, what benefit will it have been to have kept our heads buried in the sand. None.

What benefit could there be to having a theoretical discussion right now? Well, possible new ideas and approaches in the event that things should turn out poorly for our dear XMRV.

I understand that for some it brings them down, and they feel like someone is putting a turd in the punchbowl. Unfortunately life sometimes gives you turds.

You're quite right, Julius. I once won an award for making lemonade out of what others assumed were lemons. They were actually turds. but what the others didn't know couldn't hurt them.:Retro tongue:

 

[Gerwyn]

The complere sequence was characterised and compared to the viral neuclotide sequence initially characterised by the discoverer of xmrv this is what ruled out the issue of a herv and Mulv contaminant as the sequences are so different

the antibody response to the unique env region helped somewhat as well!

 

[Gerwyn]

I very much appreciate Kurt laying out in detail his ideas about XMRV and HERV's - I learned quite a bit.

The transmission question has never fully been addressed and it is an important one. Its funny how some aspects of this just go by the wayside. Anyway if XMRV is a blood borne retrovirus then I think Kurt is saying we should see regular passage from the mother to her children and between sexual partners. While we see both (Mother/children and sexual partners with CFS) both are pretty rare. This would seem to argue against an obvious viral cause of CFS.

Instead Kurt, if I got it right, lays out a theory of another breakdown in the body - first high rates of oxidative stress wiping out glutathione (Pall + VanKonynenburg?) which then results in herpesvirus activation.

The fact that the epidemiology of CFS does not - except for those outbreaks - appear to look viral - suggests that other elements must come into play. The viral trigger is certainly there, we know that - but CFS appears to be triggered by a variety of viruses (with EBV at the top of the list) as well as other stressors as well as sometimes nothing - so there's no really clear single factor. The Dubbo studies showed us that; four pathogens, if I remember correctly -which all caused CFS. This suggests that the problem has to be deeper - in something that happens in relation to the infection.

I wonder if you can fold the Dubbo projects finding of high pro-inflammatory cytokine levels in people who went on to get CFS (versus low cytokine levels in people who did not) in this scenario. In that scenario you have an infection (a stressor), high cytokine levels - then what? high rates of oxidative stress... That fits in well with Kurts scenario.

The WPI is studying family members of CFS patients. If XMRV holds up we should know if they are possibly carriers who are not ill or if they don't have XMRV at all. Certainly not all retroviruses are as infectious as HIV. Its possible - and apparently likely, if the Science study is right - that alot more people have XMRV than come down with CFS. In that scenario XMRV is infectious just not debilitating that often. That said other than the Science and Japanese study no one has found much XMRV infection in healthy controls. We had Abbott Laboratories - apparently a big diagnostic lab - unable to find any evidence of XMRV infection in several 1,000 samples of blood from healthy controls.

Another point is that even if XMRV doesn't work there is still some really exciting research going on and some pieces may be fitting together. What we need is MORE research of all kinds.

as long as everone realises the difference between an idea(speculative opinion) and a hypothesis(based on factual in vivo observations)

Everyone is perfectly entitled to express their Ideas but I have yet to read many hypotheses on this matter

 

[Stuart]

We have good analysis and bad analysis. I for one know when to call "Shenanigans!"

Some just don't know when they have lost the argument and the details are in front of their face.

This is really simple, and making it complex takes really long blathering posts.

XMRV is. It and Retroviruses will be hot items in the medical field.

XMRV is in a group of patients who have been diagnosed under Fukuda and Canadian Criteria and have multiple classic symptoms and biological signs.

In ME/CFS we have the same chicken and egg problem with all the systemic dysfunctions and infections.

There are likely people with XMRV that are not ill; there are likely people with XMRV that are ill with something but not ME/CFS.

There are likely people who are misdiagnosed with ME/CFS that are ill with something else.

There are likely people who are ill with ME/CFS that but not properly diagnosed.

It is quite possible that like the discovery that common diseases that are caused by a single gene mutation, where they thought all patients would have that mutation in the same region, they discovered there are multiple regions where a single mutation causes the same disease. Expanding this to multiple mutation illnesses you see that even common diseases with a genetic cause can be complex to map out.

ME/CFS may be illness(es) where the same (or similar) disease(s) can occur due to some hit(s) on the genome, or on some basic system process(es).

It may be not only a complex disease, but a disease complex - multiple diseases/dysfunctions. Finding XMRV and how it functions in human diseases is the best current way to tease some of this out. It is a good candidate as an explanation for causation, the varied symptoms, systemic dysfunctions, and reoccurring infections.

We know the politics of those who cashed in faking studies and creating a living off of a manipulated patient group. We also know some simply have an ideological position they are not likely to be easily swayed from.

The issue that we will have to deal with is that XMRV will be a strong focus for ME/CFS research, but what about those who are diagnosed with ME/CFS but test XMRV negative? (The need for tissue testing not just blood tests may well need addressing).

XMRV may well be causal for ME/CFS so either those who are negative are misdiagnosed with ME/CFS or they have the same or similar disease with a separate causation.

My expectation is that XMRV is a causal agent for many human illnesses. It is likely that ME/CFS is one of them. It is also likely that other insults/agents/pathogens can act to cause the same or similar disease processes. The question is, if we can differentiate them, what do we call them? Do we all have ME/CFS? Do we need a new name, or names?

I like that WPI is studying Neuroendocrine diseases and has pioneered and is focused on XMRV research. I like that PANDORA is seeking to fund NEI or Neuroendocrine Immune Centers. There are a set of chronic diseases that have many overlaps, the worst of all is the scandalous mistreatment by government agencies.

WPI is privately funded on a patient driven mission. The drivel about intentions has no basis and is a red herring argument not a red flag. The distinctions in science methodology are well documented now. There is no equivalency in the new studies. We dont need cold water or caution as a balance. We are eager for real science.

We also hope that new understanding and new working models, can aid in meaningful therapies. We hope that XMRV brings a change in government stances on research funding, medical treatments and disability regimes.

For this we have the Whittemores and Dr. Judy Mikovits to thank.

 

[parvofighter]

Shenanigans

Slam dunk Stuart. Slam DUNK!

:victory:
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