In Brief: Viruses and ME

September 30, 2013

The first in a new series of short articles attempting to explain the science behind fairly common topics and exploring how they relate to ME. This time we delve into the complex and somewhat controversial world of viruses – by Andrew Gladman.

Image shown is  a computer generated image of Rhinovirus 3. Notice in the image the 3 separate colours. Each colour corresponds to a unique protein molecule. The specialised shape of those proteins allow for the construction of a complex viral shell from only 3 separate proteins. Image courtesy of Virusworld

Computer generated image of Rhinovirus 3 capsid comprised of hundreds of copies of 3 proteins. Within this shell there is the viral genome and several functional enzymes to allow for replication of the genome and to aid the hijacking process.

I think it safe to say that no topic is quite as disputed as the role that viruses might play in the pathology of ME. Scientists, doctors, and patients all have their own opinions about how viruses could be connected to our illness: some consider viruses to be crucial elements to our disease mechanism; others consider them irrelevant to the true causation but agree they appear to act in many cases as triggers or precipitating factors; and there are those who believe the role that viruses play has yet to be adequately determined and that the evidence remains, at best, only suggestive. But let’s take a look at some of the basic concepts and consider why viruses attract so much attention in our world…

What is a virus?

A virus is generally regarded as an infectious agent, they are not thought of as living organisms as they have no means through which to reproduce by themselves, for this reason they are often classed as pseudo-living. They reproduce by invading the cells of other organisms and hijacking the cell machinery in order to produce copies of their genetic material, proteins and other structural components before assembling them into new virus particles and exiting the cell in search of new cells to hijack and further propagate themselves, this represents the sole purpose of the virus. 

Video explaining how viruses infect cells and hijack the cellular machinery for viral replication.

Video explaining how viruses infect cells and hijack the cellular machinery for viral replication.

There are millions of differing viruses in the world, with nearly every species of organism having unique viruses targeting them – there are even certain viruses that are themselves the target of viral infection! Under the broad heading of ‘virus’ there exist thousands of separate groups or viruses which are classified as taxonomically similar to all other organisms. Fundamentally all viruses are comprised of a strand of genetic material and a few small enzymes to replicate the viral genetic material to aid in the viral takeover of the cell, all of this is encased in a small protein shell known as a capsid. Each virus has unique additions to this basic structure but these thing are common to all viruses.

The groups thought most relevant to ME however are perhaps the enterovirus genus and the slightly more complex and controversial retrovirus. The fundamental difference between them lies in the route they take from first entering the cell to the initiation of viral protein production. Many viruses, like most organisms, use DNA (either a double or single strand) as their genetic material, this is generally integrated into the genetic material of the host cell by a protein and at this point the cell serves to unknowingly produce all the components required for viral replication. However, these two types – the enterovirus and retrovirus both use RNA as their genetic material.

BBC Secret Universe: The Hidden Life of the Cell episode exploring how viruses enter the cell, hijack it in order to reproduce and the immune systems response to such an invasion.

BBC Secret Universe: The Hidden Life of the Cell episode exploring how viruses enter the cell, hijack it and the immune systems response to such an invasion.

Retroviruses have a single strand of RNA as their genetic material. Within their retroviral capsid there exists an enzyme known as reverse transcriptase, the function of this enzyme is to make a copy of the RNA genome in the form of DNA. This DNA then shares the same fate as the DNA in standard viruses, being integrated into the host cell genome. The important point to make here is that this enzyme is incredibly error prone. It makes mistakes very often when copying the RNA and this means that the retroviruses mutate and evolve at a much faster rate than standard viruses and are therefore much more difficult to treat due to this. This fact is the reason why HIV is so difficult to treat. The other major difference between retroviruses and standard viruses is that retroviruses have what is known as an envelope surrounding their capsid. This is a lipid membrane stolen from the host cells membrane of the cell from with the virus originates and allows retroviruses to more easily infiltrate and hijack other cells without arousing suspicion from the immune system.

Enteroviruses are also commonly discussed in ME and some researchers believe they play an important role in the pathophysiology of our disease. Interestingly however, despite the name of this genus of virus, often they only initially reproduce within the Gastrointestinal tract before migrating to other organs or tissues such as the nervous system. They also use RNA as their genetic material, however they do not use a reverse transcriptase enzyme to convert this into DNA; therefore the viral genome is never combined with the host cell’s genome. Instead the RNA is replicated in the cell cytoplasm by an enzyme also injected into the cell by the virus particle known as RNA polymerase. The RNA has a molecule attached to one end which signals the cell machinery in the cell to initiate the start of protein synthesis, hence creating the viral proteins.  It is unusual for enteroviruses to become chronic but researchers such as Dr. John Chia believe this to be the case in ME.

Why are viruses important in ME?

It is well documented that viruses are the most common triggering factor associated with acute onset ME – both in the form of infections and through vaccinations. It is therefore easy to understand why they have perhaps attracted most research, and yet despite this they have never been conclusively shown to be the cause of the perpetuation of ME symptoms. It appears, like most areas in ME, that research is somewhat conflicted over the extent of viral involvement.

There is some anecdotal evidence from patients and doctors who have seen improvement in health and well-being while taking or prescribing antiviral treatments such as Valcyte; however more formal research on these drugs through clinical trials has yielded something of a disappointing result. Similarly researchers such as Professor Lipkin, despite their own personal view that pathogens lie at the heart of ME, struggle to find evidence of the commonly held suspects in ME; these being viruses such as EBV, CMV and HHV6 among many others. 

Attention is now turning to the possibility of a viral presence within tissue, which would allow the virus to remain undetectable by analysis of plasma and CSF samples; an example of this being the recently proposed hypothesis that viruses infected the vagus nerve. Professor Lipkin also is keen to explore the gut microbiome as this could be another location where viruses or pathogens may be lurking and adversely effecting the gut micobiota. 

As time goes on it appears that research into the association of viruses and ME is evolving and moving away from the idea that viruses are the sole causative agent. Now we are seeing increasing efforts to look more at their role in either acting as a triggering mechanism, a co-morbid problem or perhaps acting as a source of dysregulation in other areas such as the gut microbiome. One can hardly discuss viruses and ME without giving a fleeting mention to XMRV. Heralded for some time as the sole agent at the heart of the disease, the story of XMRV acts as something of a fitting metaphor for the history and state of viruses and their relation to our disease as a whole. Whilst considered at the time as a momentous breakthrough, XMRV lost it’s momentum over time as the evidence to support the hypothesis became dwarfed by the evidence against it.

Perhaps the idea of viruses as the cause of ME became so popular because it gave a simple explanation for a complex disease, but so often it is the simple explanations that are the wrong ones in medicine – with complex diseases requiring devious explanations. Certainly for some, viruses may be still be considered the true causative factor, but as time goes by and the research mounts, viruses seem to be something of a sirens song – promising answers but delivering little in return for the effort put in.

If anyone has any requests or suggestions of topics for future installments be sure to let me know in the comments below. 

Next time we delve into the up and coming hypothesis for ME – the complex topic of autoimmunity.

Further videos:

Video exploring how the genetic material of viruses itself can be recreated artificially (viriods)

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28 comments

{ 28 comments… read them below or add one }

Waverunner September 30, 2013 at 9:53 am

Great article, thank you.

My two cents. Viruses seem to be implicated in many chronic diseases e.g. asthma and Crohn's. The big problem we face is that we lack antivirals. I could get angry at this point because we have to wonder what medicine has been doing the last 50 years except suppressing symptoms but I won't. As long as we don't have working antivirals or better diagnostics, we are not able to identify the role, which viruses might play for diseases.

Now the important part. I'm quite sure, that the viruses are not the causative problem because of a very simple reason. If a virus causes disease, a lot more people should be ill by now because these viruses are masters for spreading in the right environment. In my eyes, most PWCs have a genetic defect, that causes a dysfunctional immune system, which makes them prone to pretty normal viral infections. This is a pure hypothesis but many studies point towards genetic similarities between chronic diseases and genes, which are implicated in viral infections. Unfortunately mainstream medicine is very reluctant to actually look into things, which haven't been discovered already. HIV is a perfect example. If these patients weren't demonstrating back then, nobody would have done anything and no treatment would have been developed for many years to come.

Legendrew September 30, 2013 at 10:08 am
Waverunner

Now the important part. I'm quite sure, that the viruses are not the causative problem because of a very simple reason. If a virus causes disease, a lot more people should be ill by now because these viruses are masters for spreading in the right environment. In my eyes, most PWCs have a genetic defect, that causes a dysfunctional immune system, which makes them prone to pretty normal viral infections. This is a pure hypothesis but many studies point towards genetic similarities between chronic diseases and genes, which are implicated in viral infections. Unfortunately mainstream medicine is very reluctant to actually look into things, which haven't been discovered already. HIV is a perfect example. If these patients weren't demonstrating back then, nobody would have done anything and they would be killed by the virus for many years.

Yes, it's very telling that ME doesn't appear to occur commonly in epidemics and outbreaks whereas you would expect a virally mediated disease to do so, fundamentally viruses exist for no other reason than to reproduce. I'm aware that there are a few outbreaks recorded but i suspect these are simply outbreaks of a random virus which is able to, with a high percentage chance, trigger the initiation of ME for those who have a genetic predisposition to developing the disease. This genetic predisposition is likely to occur in families and close relatives who until very recently have traditionally lived in close proximity to one another – often with whole families living with 5-10 miles of one another. Hence giving the impression of a virus being the causative agent whereas I suspect it is more likely a simple triggering factor.

To use an analogy for my opinion (and I must stress this is an opinion!); the genetic predisposition is like having petrol liberally dousing an area of forest and the virus (or anything else capable of eliciting a strong immune response) simply acts as the single spark that begins the inferno, there then seems little point trying to find the spark at this point as it's impossible to track down and of no use in quelling the ongoing fire. The 'spreading of this petrol', to continue this analogy, is likely done 2-3 years prior to developing ME symptoms as is seen in autoimmune diseases such as RA.

Waverunner September 30, 2013 at 10:39 am
Legendrew

To use an analogy for my opinion; the genetic predisposition is like having petrol liberally dousing an area of forest and the virus (or anything else capable of eliciting a strong immune response) simply acts as the single spark that begins the inferno, there then seems little point trying to find the spark at this point as it's impossible to track down and of no use in quelling the ongoing fire. The 'spreading of this petrol', to continue this analogy, is likely done 2-3 years prior to developing ME symptoms as is seen in autoimmune diseases such as RA.

Very nice analogy. The funny thing is, that asthma and other autoimmune diseases run in my family. So if CFS is based on a genetic predisposition, it would perfectly fit to what you have said and that predisposing genes run in certain families and could become a problem for the offspring.

However, I also have a big hope. Antivirals will not be an option anytime soon. I've been watching drug development for a few years now and things get worse and worse (more spending for marketing, less for R&D, no cures anywhere). Anyone who is hoping for new antivirals against adeno-, rhino- or whatever virus will find himself on a sinking ship. These drugs are mostly not developed and even if, nearly 99% fail and the rest is not very effective. It's hard to battle something, that has built in the selection pressure and evolution from the last hundreds of thousands of years.

My big hope is another thing. A healthy human body and healthy DNA also are very reliable in fighting infections. So the only solution I see, also for viral infections, is gene therapy. Next generation full genome sequencing gives us the power to find faulty genes for a reasonable price in a reasonable time. We get better at it year after year (while we DO NOT get better at drug development). So my plan is: Sequence exome or the full genome of PWCs, find the faulty genes, repair them. The nice thing about this plan is, that it can be done. There is no need for new technology or billions of dollars for drug development or 10 years of testing a drug. Gene therapy can be done today and its big advantage is, that in contrast to drug development, it gets better year after year. We have the means, we just need to use them.

Firestormm September 30, 2013 at 12:18 pm

We seem to be experiencing 'technical difficulties' with the links to video in the article above, which means 'I have cocked it up' most likely when having to reformat. Sorry about that. Normal quality service will be resumed as soon as I pull my finger out :rolleyes:

Edit:

Normal service has resumed :)

Nielk September 30, 2013 at 5:59 pm

Thanks Andrew for making a boring subject easy and fascinating. As far as genetics is concerned, my mother had Lupus and I have Crohn's. so it fits with us.

Mary Schweitzer September 30, 2013 at 7:06 pm

Several of us struggle with the beta herpesviruses – HHV-6 (generally A, but sometimes B), HHV-7, and cytomegalovirus (or HHV-5). Also, Epstein-Barr (HHv-4) clearly plays a role in triggering this disease. I'm not sure why Lipkin was so certain herpesviruses were irrelevant, but it's ignoring a lot of existing – published – research.

And (as most everybody in the community knows), I have done very well on an immune booster/antiviral. So this is not an academic subject for me. When we can keep my immune markers (virtually no NK function and the 37 kDa Rnase-L defect) and my viruses (EBV, CMV, HHv-6A, HHV-7, and Coxsackie B) under control, it also gets my symptoms under control. (for the record, I think HHV-6A has been the worst for me.). With immune and antiviral treatment, I go from a Karnovsky score of 30 to a 70.

Coxsackie B is interesting because it is in the polio family of viruses. Historically, we can trace M.E. (And therefore the Tahoe and Lyndonville outbreaks, which were outbreaks of M.E.) back to 1934, when the first recorded outbreak of "atypical polio" was recorded. Outbreaks were then referred to as "atypical polio," or sometimes Icelandic disease because of a bad outbreak in Iceland. In the UK, scientists were looking at the role of Coxsackie B in M.E, at least as far back as the 1980s.

As for autoimmunity … Well, perhaps we are talking about different subsets. Or perhaps this is one complex disease. There are many in the MS community who believe that their disease could be the result of a pathogen. Are we so sure that we really understand autoimmunity? HHV-6A appears to cause Hashimoto's thyroiditis, which is considered an autoimmune disease. And now their appears to be a form of HHV-6 that is inheritable. There is so much we don't know.

In a similar vein, we know about the outbreaks that were publicized, and many of us know about outbreaks that never were publicized – but we have no accurate count because CDC has refused to make this a reportable disease. I think we have a better sense of the outbreaks of the 1980s than any others. And I'm convinced from my inbox that we have just seen a whole new round of outbreaks.

sandra September 30, 2013 at 7:27 pm

Hi Mary,

I'm curious what are your antiviral and immune system treatments? If you don't mind sharing that it would be very helpful for me.

Thanks!
Sandra

aimossy October 1, 2013 at 3:05 am

Thanks for that article!
I am interested in the biomarkers Lipkin found and the importance/validation of these as proof and even stronger validation of ME as a physical problem.
I would love to hear an analysis on that by PR and what researchers/doctors make of this as validation.

Bob October 1, 2013 at 4:00 am
aimossy

I am interested in the biomarkers Lipkin found and the importance/validation of these as proof and even stronger validation of ME as a physical problem.
I would love to hear an analysis on that by PR and what researchers/doctors make of this as validation.

Here's a PR article on Lipkin's research, in case you haven't seen it already (But it might not answer your specific questions in detail):
http://forums.phoenixrising.me/index.php?threads/lipkin-finds-biomarkers-not-bugs.25234/

aimossy October 1, 2013 at 4:24 am
Bob

Here's a PR article on Lipkin's research, in case you haven't seen it already (But it might not answer your specific questions in detail):
http://forums.phoenixrising.me/index.php?threads/lipkin-finds-biomarkers-not-bugs.25234/

Thanks bob.
I was hoping for more in the sense that this is proof to doctors and doubters of ME having physiological basis.
What would doubters make of this?
I mean he has found biomarkers! This is a big deal in my mind!
Does the study have to be replicated.
I thought something like that would hit the newspapers.
Maybe that might happen after being published, or maybe I am hoping for too much.:)

Firestormm October 1, 2013 at 4:55 am
aimossy

Thanks bob.
I was hoping for more in the sense that this is proof to doctors and doubters of ME having physiological basis.
What would doubters make of this?
I mean he has found biomarkers! This is a big deal in my mind!
Does the study have to be replicated.
I thought something like that would hit the newspapers.
Maybe that might happen after being published, or maybe I am hoping for too much.:)

Watcha! :)

1. We need really to see a paper published. We are told it is on the way, indeed it appears likely it has been submitted and approved – else Lippers would be unlikely to have revealed all that he did in the presentation online.

2. Yep all science requires replication. There have been doubts expressed – not least by patients – about his team not finding active pathogens in the blood and spinal fluid, when it seems so many are being treated for such. So we need confirmation.

3. Lippers and his team will be searching for pathogens in tissue we are told. He didn't enlighten us as to progress and it appears ongoing; so the publication referred to above, is likely to be only part of what the Chronic Fatigue Initiative Pathogen Hunters will be trying to achieve.

4. The microbiome work is only beginning, and is in need of much more money we are told. Watch this space I guess.

5. The biomarkers found are exciting – as are all such anomalies in ME/CFS – but this is also in need of replication.

One thing is I think positive overall, and that is that this work will be regarded as high quality and has used a large (the largest?) number of patients and controls. Lippers is still thinking that a pathogen(s) are involved in the disease – he just hasn't found them or figured out how yet.

When the paper is published, be sure that Simon will be writing frantically, as I am sure will others of that :nerd:'y persuasion – thankfully :)

Legendrew October 1, 2013 at 5:37 am
Mary Schweitzer

Several of us struggle with the beta herpesviruses – HHV-6 (generally A, but sometimes B), HHV-7, and cytomegalovirus (or HHV-5). Also, Epstein-Barr (HHv-4) clearly plays a role in triggering this disease. I'm not sure why Lipkin was so certain herpesviruses were irrelevant, but it's ignoring a lot of existing – published – research.

And (as most everybody in the community knows), I have done very well on an immune booster/antiviral. So this is not an academic subject for me. When we can keep my immune markers (virtually no NK function and the 37 kDa Rnase-L defect) and my viruses (EBV, CMV, HHv-6A, HHV-7, and Coxsackie B) under control, it also gets my symptoms under control. (for the record, I think HHV-6A has been the worst for me.). With immune and antiviral treatment, I go from a Karnovsky score of 30 to a 70.

Coxsackie B is interesting because it is in the polio family of viruses. Historically, we can trace M.E. (And therefore the Tahoe and Lyndonville outbreaks, which were outbreaks of M.E.) back to 1934, when the first recorded outbreak of "atypical polio" was recorded. Outbreaks were then referred to as "atypical polio," or sometimes Icelandic disease because of a bad outbreak in Iceland. In the UK, scientists were looking at the role of Coxsackie B in M.E, at least as far back as the 1980s.

As for autoimmunity … Well, perhaps we are talking about different subsets. Or perhaps this is one complex disease. There are many in the MS community who believe that their disease could be the result of a pathogen. Are we so sure that we really understand autoimmunity? HHV-6A appears to cause Hashimoto's thyroiditis, which is considered an autoimmune disease. And now their appears to be a form of HHV-6 that is inheritable. There is so much we don't know.

In a similar vein, we know about the outbreaks that were publicized, and many of us know about outbreaks that never were publicized – but we have no accurate count because CDC has refused to make this a reportable disease. I think we have a better sense of the outbreaks of the 1980s than any others. And I'm convinced from my inbox that we have just seen a whole new round of outbreaks.

I think that there is little doubt that ME is a broad sub-heading and under it lie numerous diseases of differing pathologies however I feel the viral evidence is not prevalent or consistent enough to make it the appear the largest of the sub-groups. I agree that viruses for some could be the issue however the ongoing work looking into autoimmunity appears to be showing more consistent results for 2/3 of the patient group, however I will discuss this in greater depth in the following article!

With regard to antivirals/immunomodulators, as I previously mentioned, there is a group for whom I believe viruses to be the underlying pathology (however I suspect this may only be 15-20%) in whom these drugs may work by reducing viral load however it is also of note that these drugs could potentially have a positive effect upon an autoimmune process through disrupting the numerous cycles and pathways that would likely be involved. To my knowledge however, no trial has shown consistent and repeatable evidence for the positive effects these drugs have on ME patients as a whole. Furthermore immune abnormalities such as low NK function do not to me elude to viruses but a generalised dysfunctional immune response. Certainly a dysfunctional immune response could lead to further susceptibility to viruses but this is more an effect of the immune dysfunction and not an apparent cause. It's also interesting that many of the tests for active viruses rely on the measuring of antibody titres to the pathogen however during infection and with autoimmune conditions the immune system undergoes a process known as 'clonal expansion' where antibody numbers are increased not just to the active infection but often to many unrelated pathogens which could explain the occasional occurrence of positive tests to a plethora of different viruses.

It's also worth mentioning though that antivirals on the whole are not close to being fully effective when compared to antibiotics – this speaks to the co-evolution viruses and ourselves share. Many of the viral proteins and receptors have evolved to mimic our own to allow for them to sneak into our cells undetected and hijack it for their own means therefore it is incredibly difficult to destroy this viruses through targeted drugs. To me it appears to be quite a good thing that viruses don't seem to be the malevolent driving force behind ME as, on the whole, we have very little intervention options available to help with viruses, mostly we rely on the adaptive immune response clearing these infections up.

With regard to the outbreaks, I mentioned in my previous post a potential explanation for these however you mention that the first recorded outbreaks were only apparent in the 1930's, I think it's worth noting however that ME is not a new occurrence and similar symptom complexes have been around for hundreds if not thousands of years – to me the formal documenting of such an outbreak simply appears to show an increase in formal diagnosis. Given that viruses exist for no other reason that to reproduce I have to question whether I would expect a lot more outbreaks of ME if a virus truly laid at the heart of the condition.

To discuss MS briefly, I'm aware that there is some evidence that pathogens may be involved in the pathology of MS and i'm interested to see where this evidence leads however it is fairly well accepted that MS is down to an autoimmune process, perhaps these pathogens could be involved in this or perhaps not. I'm not sure it's of use drawing such comparisons though at this point as we're still unsure of the process at the heart of ME so it doesn't make things any clearer to muddy the water looking at MS too!

Bob October 1, 2013 at 6:10 am
Firestormm

Lippers

lol :)

(is that what is friends call him?)

Firestormm October 1, 2013 at 6:19 am
Bob

lol :)

(is that what is friends call him?)

I think it was Marco who once said I always sounded very familiar with these boffins :snigger: Having said that I don't do similarly with Professor Edwards – which is odd. I was obviously in a funny mood :aghhh: :lol:

p.s. you should ask Simon what he calls Professor Holgate :rofl:

vamah October 1, 2013 at 6:26 am
sandra

Hi Mary,

I'm curious what are your antiviral and immune system treatments? If you don't mind sharing that it would be very helpful for me.

Thanks!
Sandra

I would be interested also, as I am having trouble getting hhv 6 under control.

aimossy October 1, 2013 at 7:21 am

Thanks firestorm that was really helpful!
I have been trying to figure out for years why my WBC count is up and eosinophils and ESR and ANA (lippers talked about these) its gonna stick that knickname firestorm.:rolleyes:
I have been sent to rheumatology quite a few times because these are autoimmune markers.
Docs love their blood markers and statistics. well these are not right!!!
I was told once by someone that ME doesn't have markers so have been waiting for an autoimmune thing to flare its head worse for a loooooooong time. hahahahaha!
I didn't believe there were no biomarkers for ME just that you got put in that bracket because it really means we don't know what is up with you.
There must be a lot to have had similar thoughts of course. I have had EBV and the cat poo icky one!!!
But I never even considered that as a possible cause until a while ago and from what I've learnt from PR.
So personally from my own knowledge of human body and what I have read on here autoimmune or gut pathogen are very good paths that researchers are into.
Im glad!
I think I am maybe not the only one feeling excited like we are on the verge of good things then.
I realise we cant go of about this half cocked!
I AM VERY EXCITED ABOUT BIOMARKERS!!!!! VERY EXCITED ABOUT BIOMARKERS!:):):lol:
Jeeze I have totally outdone myself with words tonight.(please nobody burst my bubble)
night all!
I look forward to simons' writings!

aimossy October 1, 2013 at 7:30 am

actually….I am a kiwi what does watcha mean.tehe!
hopefully ill find out tomorrow.

Firestormm October 1, 2013 at 8:02 am
aimossy

actually….I am a kiwi what does watcha mean.tehe!
hopefully ill find out tomorrow.

It just means 'Hi' :)

MeSci October 3, 2013 at 3:59 am
Mary Schweitzer

As for autoimmunity … Well, perhaps we are talking about different subsets. Or perhaps this is one complex disease. There are many in the MS community who believe that their disease could be the result of a pathogen. Are we so sure that we really understand autoimmunity? HHV-6A appears to cause Hashimoto's thyroiditis, which is considered an autoimmune disease. And now their appears to be a form of HHV-6 that is inheritable. There is so much we don't know.

I'm sure there is a huge amount we don't know about autoimmunity. Research into its causes and mechanisms, and especially into treating underlying causes, seems to be at quite an early stage compared to many other disease processes.

Which makes it both exciting and exasperating!

leokitten October 21, 2013 at 2:25 pm
Waverunner

Great article, thank you.

My two cents. Viruses seem to be implicated in many chronic diseases e.g. asthma and Crohn's. The big problem we face is that we lack antivirals. I could get angry at this point because we have to wonder what medicine has been doing the last 50 years except suppressing symptoms but I won't. As long as we don't have working antivirals or better diagnostics, we are not able to identify the role, which viruses might play for diseases.

Now the important part. I'm quite sure, that the viruses are not the causative problem because of a very simple reason. If a virus causes disease, a lot more people should be ill by now because these viruses are masters for spreading in the right environment. In my eyes, most PWCs have a genetic defect, that causes a dysfunctional immune system, which makes them prone to pretty normal viral infections. This is a pure hypothesis but many studies point towards genetic similarities between chronic diseases and genes, which are implicated in viral infections. Unfortunately mainstream medicine is very reluctant to actually look into things, which haven't been discovered already. HIV is a perfect example. If these patients weren't demonstrating back then, nobody would have done anything and no treatment would have been developed for many years to come.

I do agree with you on your hypothesis, as a scientist and researcher based on what I know, the research and literature I've read, and my own disease I think viruses are not the root cause.

Just wanted to tell you there are two upcoming antivirals in late stage clinical trials which when approved by FDA for their indications will be able to be used off-label by doctors for CFS treatment. They are an improvement on the current arsenal.

CMX001 (Brincidofovir), Chimerix, Inc.

Lipid conjugate version of powerful and broad spectrum antiviral cidofovir. Unlike cidofovir it can be taken orally, has very good bioavailablity, much higher intracellular concentrations, and far reduced renal toxicity (due to the fact that the conjugate is cleaved releasing active cidofovir drug only inside cells, thus cidofovir isn't flowing around in the blood stream where it can get to kidneys and cause damage) http://www.chimerix.com/therapeutic-programs/category/cmx001

Valomaciclovir (EPB-348), Epiphany Biosciences, Inc.

Strong antiviral against many herpesviruses, looks like it might replace the much more toxic Valganciclovir for CFS treatment because it is effective against not only HSV, EBV, but also CMV and HHV-6. http://www.epiphanybio.com/

I believe these two drugs will be approved in 2015 or so and afterwards will be used off-label for CFS treatment.

SOC October 21, 2013 at 2:43 pm

That is great news, leokitten! I didn't realize that there were 3 new antivirals which should be available in 2015. That should make a big difference for some PWME.

It might be next to impossible for most ME/CFS patients to get access to those antivirals, though, because off-label use is frequently not covered by insurance and new antivirals are very pricey. Just look at the consumer cost of Valcyte. Very few of us can afford that and the new antivirals will be even more costly, I'll bet.

One thing we need is better testing and test interpretation for viruses so that more doctors properly identify chronic infections. Then the antiviral use will be for the chronic infection, for which the meds would be "on-label" and therefore covered by insurance, rather than for ME/CFS, for which antivirals are considered very much off-label and not covered by insurance.

leokitten October 21, 2013 at 3:14 pm
SOC

That is great news, leokitten! I didn't realize that there were 3 new antivirals which should be available in 2015. That should make a big difference for some PWME.

It might be next to impossible for most ME/CFS patients to get access to those antivirals, though, because off-label use is frequently not covered by insurance and new antivirals are very pricey. Just look at the consumer cost of Valcyte. Very few of us can afford that and the new antivirals will be even more costly, I'll bet.

One thing we need is better testing and test interpretation for viruses so that more doctors properly identify chronic infections. Then the antiviral use will be for the chronic infection, for which the meds would be "on-label" and therefore covered by insurance, rather than for ME/CFS, for which antivirals are considered very much off-label and not covered by insurance.

My apologies I should have been more clear… these upcoming drugs, just like Valcyte, Famvir, Valtrex, could be used by doctors off-label for chronic viral infections commonly found in CFS patients. Unless your doctor determines that your are suffering from a chronic/reactivated viral infection you should not take these medications.

"On-label" use like use say is only for the specific indications that are FDA approved.

Off-label use is any use that is not the specific indication(s) the FDA approved for the drug. For example if you have a chronic CMV and HHV-6 infection, Valcyte treatment is off-label because it is only FDA approved for AIDS-related CMV retinitis and transplant associated CMV organ disease. Insurance will still cover it because it is a "reasonable" use of the drug since your doctor believes, based on examination, symptoms, and antibody tests, that you have a chronic infection of viruses that will respond to Valcyte treatment.

Sushi October 21, 2013 at 3:24 pm
leokitten

I do agree with you on your hypothesis, as a scientist and researcher based on what I know, the research and literature I've read, and my own disease I think viruses are not the root cause.

Just wanted to tell you there are two upcoming antivirals in late stage clinical trials which when approved by FDA for their indications will be able to be used off-label by doctors for CFS treatment. They are an improvement on the current arsenal.

CMX001 (Brincidofovir), Chimerix, Inc.

Lipid conjugate version of powerful and broad spectrum antiviral cidofovir. Unlike cidofovir it can be taken orally, has very good bioavailablity, much higher intracellular concentrations, and far reduced renal toxicity (due to the fact that the conjugate is cleaved releasing active cidofovir drug only inside cells, thus cidofovir isn't flowing around in the blood stream where it can get to kidneys and cause damage) http://www.chimerix.com/therapeutic-programs/category/cmx001….

Thanks leokitten,

Earlier this year we were told that CMX001 was being "fast-tracked" and might even be available late this year. Do you have a way to check on this and let us know if 2015 is still the projected date on this drug?

Thanks,
Sushi

heapsreal October 21, 2013 at 3:40 pm

Im guessing that they will be more expensive then valcyte is right now but these drugs could drop the price of already available drugs?? That could be good for those who want to use valcyte.
I know valcyte is generic in India as they didnt obey the patent laws but anyone know when valcyte goes generic in the rest of the world?;)

leokitten October 22, 2013 at 8:20 am
Sushi

Thanks leokitten,

Earlier this year we were told that CMX001 was being "fast-tracked" and might even be available late this year. Do you have a way to check on this and let us know if 2015 is still the projected date on this drug?

No 2015 is the earliest date it can be approved, here's why:

FDA fast tracking means that after all the clinical trials are completed and results are in which show efficacy and safety then after this does an accelerated "fast track" process occur within the FDA to get the drug approved.

Chimerix just announced the study design for their CMX001 SUPPRESS Phase III clinical trial which I believe will be the last one. Results from this trial won't be in until 2015 and only after this if everything is good will the FDA fast track drug approval.

Please read more here: http://ir.chimerix.com/releasedetail.cfm?ReleaseID=789441

Data from SUPPRESS are anticipated in 2015 and, if positive, may support Accelerated Approval of brincidofovir for the prevention of CMV infection.

leokitten October 22, 2013 at 8:37 am
heapsreal

Im guessing that they will be more expensive then valcyte is right now but these drugs could drop the price of already available drugs?? That could be good for those who want to use valcyte.
I know valcyte is generic in India as they didnt obey the patent laws but anyone know when valcyte goes generic in the rest of the world?;)

I don't think you will have to wait until 2015 for cheaper Valcyte.

Technically Roche's patent for Valcyte expires in 2015, but there have already been lawsuits filed by generic firms Ranbaxy and Sandoz challenging this. I believe Roche settled out of court with Ranbaxy and Ranbaxy will get FDA approval to start making a generic version this year in 2013. But I remember reading in the news that Ranbaxy is delayed in launching the drug so lets say 2014?

As you might know since Ranbaxy was the "first to file" for generic approval they will be given 180 day marketing exclusivity for the generic version, read more here:

http://www.prnewswire.com/news-rele…nciclovir-hydrochloride-tablets-57542227.html

http://www.business-standard.com/ar…-boost-likely-for-ranbaxy-113032500013_1.html

Waverunner October 22, 2013 at 10:35 am
leokitten

I don't think you will have to wait until 2015 for cheaper Valcyte.

Technically Roche's patent for Valcyte expires in 2015, but there have already been lawsuits filed by generic firms Ranbaxy and Sandoz challenging this. I believe Roche settled out of court with Ranbaxy and Ranbaxy will get FDA approval to start making a generic version this year in 2013. But I remember reading in the news that Ranbaxy is delayed in launching the drug so lets say 2014?

As you might know since Ranbaxy was the "first to file" for generic approval they will be given 180 day marketing exclusivity for the generic version, read more here:

http://www.prnewswire.com/news-rele…nciclovir-hydrochloride-tablets-57542227.html

http://www.business-standard.com/ar…-boost-likely-for-ranbaxy-113032500013_1.html

Thanks for your comments, Leokitten. May I ask what you think about the cause of CFS? For me it seems, that CFS is a highly heterogeneous disease. Patients get labeled as PWCs very easily. CFS may be an outflow of a lack of diagnostics and a lack of molecular understanding of disease. Only a few years ago it was found out, that breast cancer is not one disease, but at least ten different diseases with distinct genetic and molecular differences. Could it be, that CFS is not one disease but hundreds of diseases? Or do you think, that CFS mostly has the same cause?

RUkiddingME November 7, 2013 at 11:52 am
heapsreal

Im guessing that they will be more expensive then valcyte is right now but these drugs could drop the price of already available drugs?? That could be good for those who want to use valcyte.
I know valcyte is generic in India as they didnt obey the patent laws but anyone know when valcyte goes generic in the rest of the world?;)

hey heaps! hope you are doing well. I'm in Canada and my insurance plan wants me to switch to the generic which became available here last month by Apotex (Canadian company)

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