New XMRV study to be undertaken.

[Marco]

Hi Bob

In my own naive way I thought this approach might give GSK the toolkit to hit retroviruses at source.

My understanding, which is probably wrong, is that retoviruses are RNA and need to 'write themselves' into cellular DNA to replicate. I also assumed that antiretroviral drugs prevent or slow replication but you are stuck with the retroviral infection for life.

Directly interfering with the RNA could kill XMRV off?

In theory?

Like this :

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WXR-4CHRYD6-2&_user=10&_coverDate=07%2F20%2F2004&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1278656559&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=032bdcbbe337a743b0f3fdd9dbd33af4

 

[Bob]

Hi Marco, I apologise, I didn't mean to sound so dismissive...
I'm no expert, so I'm sure you know more about this science than me...

This is a fascinating area of medicine that I've not really come across before...
I hadn't read that this is an area of genetic medicine that they were currently developing...

I'd heard about genetic manipulation by inserting new genes into our genetic code... but I'd not heard about the possibility of directly blocking certain strands of human RNA by using drugs, which seems more promising in the short term... i don't know why I've never heard of it... thanks for flagging it.

Retro-viruses are RNA viruses, and if a drug could block essential segments of the RNA of a retro-virus, then I imagine that the viruses would eventually die, as they wouldn't be able to function... and they wouldn't be able to replicate. It would be a novel and exciting way to treat retro-viruses.

It's really fascinating... and exciting to think that they might be thinking about developing this technology for retro-viruses... but surely they'd develop it for HIV before XMRV wouldn't they?

Hi Bob

In my own naive way I thought this approach might give GSK the toolkit to hit retroviruses at source.

My understanding, which is probably wrong, is that retroviruses are RNA and need to 'write themselves' into cellular DNA to replicate. I also assumed that antiretroviral drugs prevent or slow replication but you are stuck with the retroviral infection for life.

Directly interfering with the RNA could kill XMRV off?

In theory?

Like this :

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WXR-4CHRYD6-2&_user=10&_coverDate=07%2F20%2F2004&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1278656559&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=032bdcbbe337a743b0f3fdd9dbd33af4

 

[Marco]

Hi Marco, I'm sorry, I didn't mean to sound so dismissive...
I'm no expert, so I'm sure you know more about this science than me...

QUOTE]

Hi Bob

You didn't sound dismissive at all. The original article didn't mention retroviruses at all as you pointed out so I did a little googling. The 'naive' comment was because I'm not au fait with the science. I can just understand enough for things to catch my attention.

Reading though the 'PERV' article I'm also struck by the approach of 'ablating' or down regulating problem genes which reminded me of Kerr's gene regulation studies. To the layman like me it seems a simple step between Identifying the upregulated genes as Kerr has done and this RNA interference technology?

Any scientists out there?

 

[Gerwyn]

Hi Marco, I'm sorry, I didn't mean to sound so dismissive...
I'm no expert, so I'm sure you know more about this science than me...

QUOTE]

Hi Bob

You didn't sound dismissive at all. The original article didn't mention retroviruses at all as you pointed out so I did a little googling. The 'naive' comment was because I'm not au fait with the science. I can just understand enough for things to catch my attention.

Reading though the 'PERV' article I'm also struck by the approach of 'ablating' or down regulating problem genes which reminded me of Kerr's gene regulation studies. To the layman like me it seems a simple step between Identifying the upregulated genes as Kerr has done and this RNA interference technology?

Any scientists out there?

Hi Marco and Bob
There is nothing wrong with the grasp you have of the issues at all.Neither of you are being in the least bit niave.

There are just two points really:

The kind of RNA in viruses(prokaryotic) and that in humans is different(Eukaryotic). So the drug might bind to one and not the other.Worse still to both then the lord only knows what could happen.

This technique could work for individual gene sequences . ME/cfs,however, involves clusters of genes which co regulate each other but are a long way apart when you" unravel" the chromosome from its normal supercoiled state.its a bit like markings on a coiles rope, when coiled it looks as tho the markings are next to each other, if,on the other hand, you uncoil said rope then the markings in the uncoiled state are not close to each other at all.

 

[Bob]

I'm also struck by the approach of 'ablating' or down regulating problem genes which reminded me of Kerr's gene regulation studies. To the layman like me it seems a simple step between Identifying the upregulated genes as Kerr has done and this RNA interference technology?

This technique could work for individual gene sequences . ME/cfs,however, involves clusters of genes which co regulate each other but are a long way apart when you" unravel" the chromosome from its normal supercoiled state.its a bit like markings on a coiles rope, when coiled it looks as tho the markings are next to each other, if,on the other hand, you uncoil said rope then the markings in the uncoiled state are not close to each other at all.

Yes, that was my understanding about Kerr's work too... That there are quite a number of different genes affected in people with ME... is it about 88 or have I just plucked that figure out of the air?
Kerr has said that he has been looking for existing approved drugs that are known to be associated with the genes which he has identified in his studies.
But I think that he has found his research less helpful, or less certain, than he first expected, because instead of looking for appropriate drugs, I understand that he has now moved on with his studies and is looking at DNA 'snips' in order to gain more clarity... and I just don't understand these 'snips' at all... I don't understand his latest research or what it's aiming to achieve. (At least, i think it's called 'snips' - I'm going from memory here - which is never reliable for me!)

Reading though the 'PERV' article

lol Marco

 

[Marco]

There are just two points really:

The kind of RNA in viruses(prokaryotic) and that in humans is different(Eukaryotic). So the drug might bind to one and not the other.Worse still to both then the lord only knows what could happen.

This technique could work for individual gene sequences . ME/cfs,however, involves clusters of genes which co regulate each other but are a long way apart when you" unravel" the chromosome from its normal supercoiled state.its a bit like markings on a coiles rope, when coiled it looks as tho the markings are next to each other, if,on the other hand, you uncoil said rope then the markings in the uncoiled state are not close to each other at all.

Thanks Gerwyn - that's what I thought!

Seriously though, and without wishing to further divert this thread :

As to point 1, doesn't the fact that the RNA types differ between animals and viruses make it easier to specifically deliver any drug therapy?

As for point 2, I see the problem, and I recall that Kerr identified 88 genes. Does this imply that, at present, this type of RNA interference therapy is limited only to those diseases where only one or a few closely related genes are involved?

 

[Gerwyn]

Thanks Gerwyn - that's what I thought!

Seriously though, and without wishing to further divert this thread :

As to point 1, doesn't the fact that the RNA types differ between animals and viruses make it easier to specifically deliver any drug therapy?

As for point 2, I see the problem, and I recall that Kerr identified 88 genes. Does this imply that, at present, this type of RNA interference therapy is limited only to those diseases where only one or a few closely related genes are involved?

Hi Marco,
For what it is worth it would be better looking at the regulatory processes than the genes themselves because the "switches" have a great deal of commonality while the genes themselves do not.In short why are they upregualted and what causes this upregulation? . RNA therapy involving coregulating genes has not been demonstated thus far--but who knows perhaps even tomorrow?This research area moves so fast!

As to point one AZT was thought to be specific to reverse transcriptase look what happened

 

[Cookie Monster]

I've found the articles where I read about it:

http://www.newscientist.com/article/dn18442-drug-for-depression-tried-on-stressedout-rats.html

http://www.newscientist.com/article/mg17022954.600-a-mind-under-siege.html

Subquote " ...They suggest that some people who are depressed may actually be suffering from an over-heated immune system, and that damping down inflammation could offer a brand new way to treat routine clinical depressionwhile making billions for the pharmaceuticals industry into the bargain. It's a theory that recasts depressionone of the great plagues of our timeas a chronic inflammatory disease like rheumatoid arthritis.
The first inkling of a connection between mood and inflammation came around 1990. Michael Maes, a psychiatrist now at the University of Maastricht in the Netherlands, was investigating claims that depressed people are unusually vulnerable to infections and cancer, a theory that could be explained by a lacklustre immune system. But when Maes looked at immune cells from depressed people such as natural-killer cells, monocytes and macrophages, he found instead that the cells were more active than normal, and spewed out more inflammatory cytokines. "We had expected to find just the opposite," admits Maes."

:Sign Good Job: *interestingly....the prevalence of rheumatoid arthritis in the general population i believe is roughly about 4%...a familiar percentage ? (ie same as those found in the Science article to be XMRV+ve in the healthy controls) although maybe/probably just a coincidence

Given that cytokines often have been mentioned in the same sentence as ME (see quote below from telecon discussion between Dr Mikovits and Dr Cheney), does this mean that cytokine inhibitors may be a potential treatment for both this disease and depression?

Cheney: "In the Lake Tahoe epidemic many years ago, but also here in my clinic in Ashville, we frequently see an elevated CD4 to CD8 ratio, primarily due to CD8 depletion, and I wonder if you might comment. Is CD8 depletion something that XMRV might be able to cause?"

Mikovits: "We dont see XMRV as a cytotoxic virus, thus far. Certainly, it is possible through indirect effects, through mediators or whats known as cytokines, we could see dysregulation of the adaptive immune response which is the CD8 cell. But we dont see direct cytopathic. More this virus seems to be like HTLV-1 and not kill its cells like HIV."

Could anyone please tell me if the indirect CD8 cell dysregulation (as described above) still fits in well with the pattern of changes in the balance between IL(interleukin)10 and IL12 levels seen by Dr Cheney in ME patients & described in the following article? Would be good to think everything seems to fit together in some way but im definitely lacking in the knowledge department to be able to make a call on that

http://www.anapsid.org/cnd/diagnosis/cheneyis.html

 

[Noreen Martin]

Everyone is right, no drug company in their right mind will miss this chance to make tons of money. I can only see two immediate problems, one being studies will have to be done before doctors will feel comfortable in prescribing drugs and secondly, whatever drug or drug combinations they develop will be very expensive. They will want to make as much money as possible in the first seven years. But on the bright side, patients in the long run will benefit from these medicines!

 

[fred]

Could anyone please tell me if the indirect CD8 cell dysregulation (as described above) still fits in well with the pattern of changes in the balance between IL(interleukin)10 and IL12 levels seen by Dr Cheney in ME patients & described in the following article? Would be good to think everything seems to fit together in some way but im definitely lacking in the knowledge department to be able to make a call on that

And also how it fits with this from Cort's write up of the Dr Light presentation.

"Interestingly, given all the interest in pro-inflammatory cytokine levels, neither of the two cytokines tested (IL-6, IL-10) exhibited increased activity in the ME/CFS patients. The activity of the anti-inflammatory cytokine IL-10, which appears to be showing up again and again in ME/CFS studies, was increased."

http://www.ei-resource.org/columns/...tes-increases-after-moderate-exercise-in-cfs/

 

[dmarie4301]

Funkmaster: Im not sure if Im up for the debate. I dont have any sources.

I finally found my source: www.vactruth.com. There's SO much info on that website....TMI! The age of information. Too much to read, wish I could just download it into my head, instead of having to sit at the computer and read, and focus. Im not lasting long today. Was trying to read natasha's posting from Dec about Mice being used in vaccine production...that did me in!

Anyway, just wanted to get back on that. There's SO much info on vaccines and illness, like our newcomer mom whose daughter got sick after the Gardisil vaccine.

A friend of mine, was a nurse, struggling with fibro, and her boss insisted she get the H1N1. So she finally did...took her out...she got Sjorgens syndrome, had to quit work, and now is up against how to take of yourself when you are too sick to get off the couch. I and she believe that Swine flu vaccine pushed her over the edge.

I wont touch a vaccine. I wouldnt be a bit surprised that contaminated vaccines is how we all got these illnesses. Actually I do believe it. Science creating the Frankenstein all over again. Do you all know that a few years back they made a flourescent rabbit??? By adding in genes from one species into another, they create new things. Like taking DNA from cold water eels, inject into tomatoes, so they withstand frost. Now we're talking Genetically Modified foods.....but it's all bad in my opinion.

 

[Cloud]

Vaccines themselves reactivate latent viruses.

Apparent contamination can just mean that the reactivated virus can be detected where it could not be before .

Proliferation then causes a rise in titre sufficient to cause symptom.

I wonder if the Glaxo microbiologists found a hitherto unidentified retrovirus in one of their test subject's blood and have put two and two together.This time making four!

Precisely what I believe happened to me since I became ill immediately following Hep B vaccine and had no other obvious acute triggers, such as infection. I believe it was latent xmrv that was activated by the vaccine. But I also believe vaccine to be more than just a trigger in this neuroimmune epidemic; I believe we shall soon see it to be a much bigger player than that. But I don't believe contaminated vaccine damage control to be GSK's motivation for this study. It's all about the bottom line.....there is potentially truckloads more money involved in an infectious rather than psych cause of ME/CFS, FM, Autism, MS, GWS.......Not to mention that most of us can't tolerate anti depressants and other psych meds anyhow. I think GSK being on board is deserving of celebration. This is what we have been waiting for.....big money/power on our side.

I was entered into this study I believe as one of the positive controls. I am happy to contribute in any way possible to our community, but I also believe it will lead to clinical trial with drugs. GSK = drugs. Also, the ultimate "validation" study will be responsiveness to anti retrovirals, so I am hoping to participate in that capacity as well. Best of all everyone....we are months, not years away from the answers! Cartwheels indeed!!!!

 

[jimbob]

Great update cloud! Hopefully we'll be well enough in the near future to actually do cartwheels.

 

[omerbasket]

Cloud, it would be fantastic if you would be able to update us when you have some information regarding this study (where it stands, when its supposed to be finished an published, what are the results, what they asked you to do, what did people there tell you etc.). I mean, I guess most of these things would be impossible for you to know - but if you do know something that might be even somewhat interesting - please, inform us, if you can.

And good luck to you and to us as well.

 

[Cloud]

jimbob....I was thinking we got to have a huge celebration when we get to the finish line. We are a community of people scattered all over the planet, but maybe there will be a way to get together in centralized groups celebrating! I couldn't do a cartwheel before becoming ill, but I sure will try now!

Omerbasket.....So far, I've just been plugged in and waiting for instruction...but you bet I will share everything. I'm expecting to see several of us on here talking about this study and hopefully it's evolution into clinical trial real soon. Lets keep this thread going!

 

[omerbasket]

Do you know when will the blood draws start?

 

[jimbob]

I definately don't want to lose touch with everyone once we turn the corner. hopefully we can keep this site or start another one to talk about all the good things happening?!

 

[Bob]

Precisely what I believe happened to me since I became ill immediately following Hep B vaccine and had no other obvious acute triggers, such as infection.

Hi Cloud, That's interesting... One of my possible triggers was Hep B vaccinations... I was working in a hopital, and I had to have Hep B vaccinations to work there... They kept on checking my Hep B antibody levels and they were not high enough, so I had 3 Hep B vaccinations in total in order to raise the antibody levels... There were other possible factors for me as well... such as working in a hospital... but the Hep B vaccines do seem like quite a significant factor... especially as I had three of them.

 

[Cookie Monster]

Hi Cloud, That's interesting... One of my possible triggers was Hep B vaccinations... I was working in a hopital, and I had to have Hep B vaccinations to work there... They kept on checking my Hep B antibody levels and they were not high enough, so I had 3 Hep B vaccinations in total in order to raise the antibody levels... There were other possible factors for me as well... such as working in a hospital... but the Hep B vaccines do seem like quite a significant factor... especially as I had three of them.

Hi Bob, im wondering if you have seen this month's poll on the ME Association's website. Its specifically about whether people feel their ME was triggered by vaccination, and if so, which one. Out of 444 replies to date, Hep B has received approx 60% of the votes - its way way out in front.

http://www.meassociation.org.uk/ind...-by-a-vaccination-which-vaccine-was-involved

 

[Overstressed]

Hi Bob,

that's interesting, because I know that a German researcher, F.Meyer, started a company, '3d antisensetec', claiming to have an HIV vaccine ready in 7 years, if he get's the money together(20 mio Euro's). He claims not only eradicating HIV, but all kinds of viruses through antisensing.

Grtz,
OS.