XMRV Study No. 4

[Esther12]

I know that others here are better informed about this subject than I am, but given how little we still know about XMRV, this discussion seems a little premature. From what little we know, I don't think we're going to be able to sensibly extrapolate whether XMRV and CFS is linked, or even likely to be linked - we're going to have to wait and see what the replication studies say.

So far three against and not one in favour is looking a bit ominous, whatever the flaws there may be with the three negatives (you'd have thought we'd have heard something if others were finding the WPI's results easy to replicate). The WPI don't seem concerned, but we'll have to wait and see if their confidence is well founded. I really hope it's not a bust, but I don't think there's any point getting too commited to this link panning out yet.

 

[kurt]

It does, actually.

Touch

I guess I walked into that one...

'Reported by some patients' and not all, however, still leaves open the possibility that these are common symptoms in a class of diseases. Again, overlapping signs and symptoms like this suggests a common pathology, but we need more data to know what are the common causes. Given that many of these symptoms also appear in Lyme Disease and other pathologies with no known exogenous retroviral involvement, I think we are still just speculating.

 

[bel canto]

Good points. After studying the methylation hypothesis for CFS (which I think may be very close to the truth, but maybe not the whole story) I have seriously wondered if CFS is simply an adult-onset subset of autism, there is a lot of evidence to support that in the pathology.

ADULT-ONSET AUTISM? REALLY? Isn't autism by definition a "developmental" disorder? And doesn't adult by definition mean already "developed"?

 

[Robin]

ADULT-ONSET AUTISM? REALLY? Isn't autism by definition a "developmental" disorder? And doesn't adult by definition mean already "developed"?

Yeah!

I agree, the autism/CFS comparisons are brought up quite a bit but always seem totally wrong to me. This shares absolutely nothing with my experience of ME/CFS.

 

[kurt]

ADULT-ONSET AUTISM? REALLY? Isn't autism by definition a "developmental" disorder? And doesn't adult by definition mean already "developed"?

Yeah!

I agree, the autism/CFS comparisons are brought up quite a bit but always seem totally wrong to me. This shares absolutely nothing with my experience of ME/CFS.

I said a SUBSET, not adult autism. Autism is a spectrum disorder (ASD), from high-functioning Asperger's (think Albert Einstein), to ADD/ADHD to the incommunicative form. And the theory that suggests CFS could be a subset, on the ASD spectrum has to do with some common methylation defects (Genetic) found in both. The difference being when the trigger events occur, if they occur later in life, then rather than causing developmental problems, the condition expresses relative to the developed state of the adult.

 

[Knackered]

I said a SUBSET, not adult autism. Autism is a spectrum disorder (ASD), from high-functioning Asperger's (think Albert Einstein), to ADD/ADHD to the incommunicative form. And the theory that suggests CFS could be a subset, on the ASD spectrum has to do with some common methylation defects (Genetic) found in both. The difference being when the trigger events occur, if they occur later in life, then rather than causing developmental problems, the condition expresses relative to the developed state of the adult.

I think we're delving in to the realms of fantasy with this one.

I think part of the problem with certain people not understanding our symptoms is people with the same illness not understanding our symptoms.

 

[bel canto]

I said a SUBSET, not adult autism. Autism is a spectrum disorder (ASD), from high-functioning Asperger's (think Albert Einstein), to ADD/ADHD to the incommunicative form. And the theory that suggests CFS could be a subset, on the ASD spectrum has to do with some common methylation defects (Genetic) found in both. The difference being when the trigger events occur, if they occur later in life, then rather than causing developmental problems, the condition expresses relative to the developed state of the adult.

"Subset" of a category means, by definition, something within that category. And autism is a developmental disorder, so cfs cannot be classified as a subset, by DEFINITION. If you are going to expound on these "theories", at least be precise in what you are trying to say.

Maybe you are trying to talk about the theory that these conditions are both subsets of an underlying genetic disorder, and the differences arise from the timing of some later "trigger". That would also be consistent with a viral exposure. Both of these conditions (CSF and autism) are so complex, however, and present with such wide variations within the defined labels, that this comment adds nothing to our understanding.

 

[julius]

I have asperger syndrome, diagnosed by a psychiatrist. Also diagnosed by a MD as having CFS. Both diagnoses were made using the same set of symptoms. I know a bit about both conditions. When I heard Dr Mikovits mention autism being possibly related to XMRV I had exactly the same thought as Kurt. It is a reasonable theory, and it fits with all symptoms of both diseases. I won't go any more into detail, because I think Kurt said it correctly already. Unfortunately, there seems to be a condition on this forum that causes people to become illiterate when reading Kurts posts.

 

[Gerwyn]

I have asperger syndrome, diagnosed by a psychiatrist. Also diagnosed by a MD as having CFS. Both diagnoses were made using the same set of symptoms. I know a bit about both conditions. When I heard Dr Mikovits mention autism being possibly related to XMRV I had exactly the same thought as Kurt. It is a reasonable theory, and it fits with all symptoms of both diseases. I won't go any more into detail, because I think Kurt said it correctly already. Unfortunately, there seems to be a condition on this forum that causes people to become illiterate when reading Kurts posts.

People diagnosed with autism must display the triad of impaiments.

These are not in the symptom range of ME.There is evidence of psuedogene activity in autism.Adult onset autism occurs after a brain insult although some people escape diagnosis untill adulthood.

ME and autism may well share the same causative ageant though.

The diagnosis of ASD is made according to the presence or abscence of the triad not on a wider symptom complex.

If done otherwise the diagnosis is incorrect.A number of other conditions mimic ASD.

When communication regarding matters of science it is helpful,for the sake of clarity. to avoid intertwing fact with supposition,belief and anecdotes.

The triad of impairments

The whole spectrum is defined by the presence of impairments affecting social interaction, communication and imagination. This is known as the triad of impairments. This is always accompanied by a narrow repetitive range of activities.

*
Social interaction

Problems engaging in reciprocal social interactions
A severely affected individual will seem aloof and uninterested in people where someone less affected (but still affected) passively accepts social contact, even showing some pleasure in it, though he/she does not make spontaneous approaches.
*
Social communication

A lack of appreciation of the social uses and the pleasure of communication is always present in some form or other
A significant proportion of people with classic autism fail to develop useful speech. If language is used, there is a failure to understand that it is a tool for conveying information to others. Some ask for their own needs but have difficulty in talking about feelings or thoughts and in understanding the emotions, ideas and beliefs of other people.
*
Social imagination

Inability to play imaginatively with objects or toys or other children/adults
Pretend play can be absent or repetitive. A tendency to select for attention minor or trivial aspects of things in the environment instead of an imaginative understanding of the meaning of the whole scene is often found. Some imaginative activities may be displayed but these are usually copied, for example from TV programmes. This play may seem complex, but careful observation shows its rigidity and stereotyped nature.

 

[natasa778]

these impairments are surface manifestations of biomedical problems so don't really mean anything, or add anything, to the discussion on the etiology or physiology of the disorder.

that definition above is full of myths, I would not even know where to start. every single sentence is full of incorrect statements and "yes BUT".

just as an example, I know of a very severely affected boy (the most severely autistic I've met actually), he is 8 and completely non verbal, still in nappies, very poor play or imagination BUT this boy craves social contact, he is very interested in other children, he WANTS to interact and he actively seeks interaction. yet all that comes out and shreeking sounds and handflapping.

The triad of impairments is written by psychobabble 'scientists' (there are many many Wessley clones in the world of autism, making a nice living by wasting precious money and time). The description above is helpful in terms of helping get some form of diagnosis but the diagnosis itself does not mean a thing anyway!! Stripped down to details and translated into the real world, it is psychobabble after all

 

[Gerwyn]

these impairments are surface manifestations of biomedical problems so don't really mean anything, or add anything, to the discussion on the etiology or physiology of the disorder.

that definition above is full of myths, I would not even know where to start. every single sentence is full of incorrect statements and "yes BUT".

just as an example, I know of a very severely affected boy (the most severely autistic I've met actually), he is 8 and completely non verbal, still in nappies, very poor play or imagination BUT this boy craves social contact, he is very interested in other children, he WANTS to interact and he actively seeks interaction. yet all that comes out and shreeking sounds and handflapping.

The triad of impairments is written by psychobabble 'scientists' (there are many many Wessley clones in the world of autism, making a nice living by wasting precious money and time). The description above is helpful in terms of helping get some form of diagnosis but the diagnosis itself does not mean a thing anyway!! Stripped down to details and translated into the real world, it is psychobabble after all

i,m not denying the biochemical abnormalities.

I would expect them in any mitochondrial disorder.

My point related to a claim that autism can be diagnosed on a plethora of surface symptoms.It cant.

The core impairments are a poor relection of underlying abnormalities there is no doubt about that

When faced with very similar surface symptoms doctors resort to differential diagnosis.

If one doctor faced with a constellation of symptoms diagnoses Aspergers and another faced with the same presentation diagnoses ME the one of them has got it wrong!

The triad forms the core of the differential diagnosis developed by experts in the field over many years ,not psychos , but mainly pediatric neurologists and clinical psychologists.

It is an objective constant measure which seperates people with psychiatric and other neurological conditions.

ASD is a neurological condition associated with mitochondrial dysfunction.There are many recognised causes of Mito dysfunction toxins,parasites,bacteria,prions and VIRAL infections

 

[natasa778]

I suspect in many cases 'psychatric conditions' may be have to be reconsidered

this one resonates on many levels:
Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder http://www.hindawi.com/journals/cpn/2009/278531.html

esp interesting in the light of recent postings on microglial inflammation, as well as blood flow to the brain

 

[Gerwyn]

I suspect in many cases 'psychatric conditions' may be have to be reconsidered

this one resonates on many levels:
Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder http://www.hindawi.com/journals/cpn/2009/278531.html

esp interesting in the light of recent postings on microglial inflammation, as well as blood flow to the brain

Yes i should have said"psychiatric".I was really referring to attachment maladaptations that so closely mimic aspergers particularily the avoidant ones.They used to be called narcisistic personality disorders.I dont like the term because it is perjorative and implies fault where there is non.The Romanian orphan examples are broadly thr kind of thing that I,m talking about

 

[julius]

The theory that I was talking about was what I thought Kurt had brought up which is this (assuming a common aetiology, let's say 'X' here for the sake of argument);

1) You get 'X' at a young age, before the age of 3-4. In this case, the effects on cognition/neurology lead to the developmental deficits known as autism. As well, you get the whole host of physical symptoms.

or

2) You get symptomatic 'X' at a later age. Here, you have passed a 'developmental threshold' and don't show the classic developmental deficits. Your symptoms in this case could be called CFS. Or, in the case of this theory, adult (late) onset autism.

Discussing this may not seem appropriate for members who experienced a later onset of CFS, but for those of us who had an early onset it is not only interesting but could be very informative.

And it is also very important to consider that the current definition of 'autism' is a DSM definition, and therefore not worth the paper it's written on. Natasa was correct in this point. Personally I am not even convinced that asperger is actually in the same category as classical autism. They seem like two different conditions with some tenuously drawn similarities.

And one other interesting point. Did any of you guys read the thread about the CDC Autism 'researcher' who just absconded with millions of dollars.
http://www.forums.aboutmecfs.org/sh...in-CDC-Vaccine-Cover-Up-Absconds-With-2M-quot
This stuff blows my already blown mind.

 

[Jenny]

A lot of researchers are interested in the similarities between autism and ME. RichvanK is one; Amy Yasko is another. They draw on complex theories about genetic predispositions and methylation processes.

Interesting stuff.

Jenny

 

[Gerwyn]

The theory that I was talking about was what I thought Kurt had brought up which is this (assuming a common aetiology, let's say 'X' here for the sake of argument);

1) You get 'X' at a young age, before the age of 3-4. In this case, the effects on cognition/neurology lead to the developmental deficits known as autism. As well, you get the whole host of physical symptoms.

or

2) You get symptomatic 'X' at a later age. Here, you have passed a 'developmental threshold' and don't show the classic developmental deficits. Your symptoms in this case could be called CFS. Or, in the case of this theory, adult (late) onset autism.

Discussing this may not seem appropriate for members who experienced a later onset of CFS, but for those of us who had an early onset it is not only interesting but could be very informative.

And it is also very important to consider that the current definition of 'autism' is a DSM definition, and therefore not worth the paper it's written on. Natasa was correct in this point. Personally I am not even convinced that asperger is actually in the same category as classical autism. They seem like two different conditions with some tenuously drawn similarities.

And one other interesting point. Did any of you guys read the thread about the CDC Autism 'researcher' who just absconded with millions of dollars.
http://www.forums.aboutmecfs.org/sh...in-CDC-Vaccine-Cover-Up-Absconds-With-2M-quot
This stuff blows my already blown mind.

autism is defined under IC 10 F84 as a neurodevelopmental disorder--That is the WHO position.I agree that both could have an infective ageant as common cause.Both have evidence of mitochondrial dysfunction but so do many other quite seperate diseases.No one will give a differential diagnosis of autism without the triad they exist irrespective of age.Late onset autism is unknown other than post trauma.many escape diagnosis untill adulthood.Mitochondrial insult could in theory cause similar symptoms though.

 

[kurt]

I think we're delving in to the realms of fantasy with this one.
I think part of the problem with certain people not understanding our symptoms is people with the same illness not understanding our symptoms.

There is no question that there are many 'factions' in the research world about the causes of CFS. So I don't think there is any surprise that there are also factions with varying beliefs and understanding of ME/CFS among patients. But which patients have it right? Finger-pointing to other patients and saying that they don't understand their illness is not very constructive in this discussion. Nobody has the answers yet, if they did we would not be having this conversation.

I have asperger syndrome, diagnosed by a psychiatrist. Also diagnosed by a MD as having CFS. Both diagnoses were made using the same set of symptoms. I know a bit about both conditions. When I heard Dr Mikovits mention autism being possibly related to XMRV I had exactly the same thought as Kurt. It is a reasonable theory, and it fits with all symptoms of both diseases. I won't go any more into detail, because I think Kurt said it correctly already. Unfortunately, there seems to be a condition on this forum that causes people to become illiterate when reading Kurts posts.

Yes, it is reasonable, and I am not saying it is a perfect fit, clearly adults with ME/CFS are not autistic in the classical sense, but over time as researchers untangle the underlying pathology of ASD conditions they have broadened the definitions and who knows where it all fits together. There seem to be common elements between ME/CFS and a number of other diseases as well, like we are all on a large Venn Diagram with overlaps between multiple groups. We have talked about AIDS, and now ASD conditions.

Here is another example, if we were to consider Lyme Disease the comparison would also be compelling, there are people who say we all have Lyme. In fact there was one lab, I believe called Bowman, in Florida, that at one time held that Lyme Disease had become ubiquitous, their tests were showing high percentages of Lyme infection in the general population. But eventually that got discredited and they were sued by some patients and went bankrupt, although I believe they reorganized as a different lab and are promoting their Lyme antigen test again, but keeping a lower profile. I had that test and for a long time believed I had Lyme, and some of the Lyme treatments were harmful to me, probably due to poor detox capacity and the lower circulation due to the CFS, maybe that experience sensitized me to be more careful in the future, about XMRV or really ANY bold new claim about ME/CFS. But the fact remains, there is a LOT of symptom and biological overlap between Lyme and CFS.

The theory that I was talking about was what I thought Kurt had brought up which is this (assuming a common aetiology, let's say 'X' here for the sake of argument);
1) You get 'X' at a young age, before the age of 3-4. In this case, the effects on cognition/neurology lead to the developmental deficits known as autism. As well, you get the whole host of physical symptoms.
or
2) You get symptomatic 'X' at a later age. Here, you have passed a 'developmental threshold' and don't show the classic developmental deficits. Your symptoms in this case could be called CFS. Or, in the case of this theory, adult (late) onset autism.
Discussing this may not seem appropriate for members who experienced a later onset of CFS, but for those of us who had an early onset it is not only interesting but could be very informative.
And it is also very important to consider that the current definition of 'autism' is a DSM definition, and therefore not worth the paper it's written on. Natasa was correct in this point. Personally I am not even convinced that asperger is actually in the same category as classical autism. They seem like two different conditions with some tenuously drawn similarities.

Yes, that is exactly what I was trying to say, thanks.

A lot of researchers are interested in the similarities between autism and ME. RichvanK is one; Amy Yasko is another. They draw on complex theories about genetic predispositions and methylation processes.
Interesting stuff.

Yes, this is clearly an emerging trend, Rich even has one clinical study now that was presented in the Reno CFS conference last year, showing significant improvements in a group of CFS patients. And Sarah Myhill is another researcher (in the UK) who is now supporting this methylation pathology viewpoint, in conjunction with her mitochondria approach. What I really like about this theory is how it ties so many parts of the pathology together.

What I don't like about the current methylation theory is the light coverage of the predisposing factors, in particular, lack of thorough analysis of the glutathione load factors that lead to the eventual depletion and methylation cycle block. Viral, bacterial, toxins, even trauma and stress, all add to the glutathione load. Then RNasL, various immune and detox SNPs, and nutrient-limiting dysbiosis (enteroviruses?) reduce the ability of the body to limit the glutathione load factors directly. Then there is the probable Herpes reactivation which depletes glutathione further (studies show herpes depletes glutathione at a high rate). So with this high glutathione load, over time we become overwhelmed with oxidative stress, which breaks down the mitochondria function. A very interesting theory with pretty good evidence.

 

[Gerwyn]

There is no question that there are many 'factions' in the research world about the causes of CFS. So I don't think there is any surprise that there are also factions with varying beliefs and understanding of ME/CFS among patients. But which patients have it right? Finger-pointing to other patients and saying that they don't understand their illness is not very constructive in this discussion. Nobody has the answers yet, if they did we would not be having this conversation.

You are either suffering from ASD or not

The core symptoms dont occur in ME.

Glutathione depletion occurs in Aids as a direct effect of the virus .A block in the methylation cycle is one of many possible causes of glutathione depletion

it is also common in other chronic viral infections.

These patients dont develop ME .

Retroviruses can directly interfere with DNA methylation ,acting as on off switches , and directly reduce glutathione in these instances these observations are an effect rather than a cause.

The cause which sets off this chain of events in this scenario is a retroviral infection.

The majority of patients recieve little or no benefit .with the glutathione treatment protocol why? because something is continually and actively depleting the glutathione levels.

An inserted retrovirus acting as a pseudogene inducing polymorphism or affecting gene regulation would be consistent with this observation

If low glutathione is causative then replacement should theoretically eliminate the symptoms and we have a problem with accounting for other reported observations as well such as interferon levels tgfb1 etc

 

[kurt]

Glutathione depletion occurs in Aids as a direct effect of the virus. it is also common in other chronic viral infections. These patients dont develop ME .

I have been saying this for some time (that AIDS patients do not develop ME/CFS). But yes, glutathione depletion may have varying levels of severity, and there may be other co-factors for developing ME/CFS.

Retroviruses can directly interfere with DNA methylation and directly reduce glutathione in these instances these observations are an effect rather than a cause.
The cause which sets off this chain of events in this scenario is a retroviral infection.
The majority of patients recieve little or no benefit .with the glutathione treatment protocol why? because something is continually and actively depleting the glutathione levels.
An inserted retrovirus acting as a pseudogene or affecting gene regulation would be consistent with this observation
If low glutathione is causative then replacement should theoretically eliminate the symptoms and we have a problem with accounting for other reported observations as well

This is also something I have tried to say repeatedly, but there is more. The lowered glutathione sets the stage for continued viral and probably also any retroviral activation. Then toxins build up, eventually blocking glutathione production itself. So the effect becomes the cause, it creates a vicious cycle. The major point we are differing on in this context is that I believe herpes activation alone can cause this scenario, if it coincides with some other preconditions (perhaps enterovirus) and is able to activate a HERV such as K18.

Yes a retrovirus is one possible factor in glutathione/methylation cycle problems, if its pseudogene activity targeted some critical step in the methylation cycle. However, if that were the case then more than likely everyone infected with that retrovirus would go on to develop CFS.

Actually a majority of CFS patients using methylation support experienced some benefit, per the study reported at the Reno conference. Several who used methylation support in conjunction with other therapies recovered enough to return to work. I believe that is critical, to address the factors depleting the glauthione along with the methylation cycle problem itself. So I agree completely that if the gluathione explanation is correct then understanding the glutathione load and reducing that is critical. Maybe even more important than directly treating the broken methylation cycle. And a retrovirus as part of glutathione load makes more sense to me than direct interference in the cycle. If a retrovirus interfered directly then all infected would contract CFS. Whereas , if a retrovirus is just part of glutathione load then those with SNPs in the methylation cycle would be more affected, most carriers would not be sick. Anyway why not treat the whole pathology, both reduce glutathione load dramatically, lowering oxidative stress, and also support the SNPs with the 'genetic bypass' approach promoted by Yasko and Rich VanK. That is what those who are recovered may have done in Rich's study.

Also, if ME/CFS is a glutathione overload condition (meaning too much load on glutathione production), then there may be many diverse load factors and triggers, more than just one virus or retrovirus, which is consistent with experience of this disease. Retroviruses for some, herpes reactivation for some, multiple co-infections, trauma, chronic stress in a person with pain/fatigue receptor vulnerabilities, all types of possibilities for that load.

Just supplementing glutathione does not always help because that is a large molecule that is hard to absorb. Also I believe in some cases it must be produced inside human cells, and it has some rate limiting production factors so increasing levels is complicated. Thus the need to 'unblock' the methylation cycle problems to get cells to produce their own glutathione again and stop the continual mitochondria damage from the oxidative stress.

Note that increasing cellular glutathione improves survival chances in AIDS, and slows viral replication. We could argue about the reasons, I suspect it helps by slowing co-infection activity, but maybe it also slows retroviral activity. If XMRV is proven to be part of the CFS pathology I also suspect that glutathione/methylation cycle support will be one of the preferred treatments due to relative safety and inability of ART to significantly alter disease course in a slow replicator retrovirus. However, apparently the unique SNPs of CFS patients MUST be taken into account, so just going to an alt med doc and saying you need to boost glutathion may be counterproductive, as most docs do not know about the common sulfur processing problems and the complex liver detox issues most of us have. So some program like Rich's approach may make a lot of sense, combined with adjunct treatments that can help reduce total glutathione load.

 

[dannybex]

Glutathione load / depletion ?

Also, if ME/CFS is a glutathione overload condition, then there may be many diverse load factors and triggers, more than just one virus or retrovirus, which is consistent with experience of this disease. Retroviruses for some, herpes reactivation for some, multiple co-infections, trauma, chronic stress in a person with pain/fatigue receptor vulnerabilities, all types of possibilities for that load.

Note that increasing cellular glutathione improves survival chances in AIDS, and slows viral replication. We could argue about the reasons, I suspect it helps by slowing co-infection activity, but maybe it also slows retroviral activity. If XMRV is proven to be part of the CFS pathology I also suspect that glutathione/methylation cycle support will be one of the preferred treatments due to relative safety and inability of ART to significantly alter disease course in a slow replicator retrovirus.

Hi Kurt,

Okay...now I'm confused (even more than usual!).

You use the term 'glutathione overload'. Isn't it Rich's hypothesis that ME/CFIDS is due to possible methylation blocks and glutathione depletion?

Thanks in advance,

Dan