Raltegravir inhibits murine leukemia virus: implications for chronic fatigue syndrome

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George

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Nice little piece of research here.

http://www.virology.ws/2009/11/20/raltegravir-inhibits-murine-leukemia-virus-implications-for-chronic-fatigue-syndrome/

Quick quote from the article

The finding that a retrovirus, XMRV, is associated with chronic fatigue syndrome has lead to the suggestion that the disease might be treated with some of the antiviral drugs used to treat AIDS. The integrase inhibitor Raltegravir has been found to block the replication of murine leukemia virus, which is highly related to XMRV. But the drug exacerbates autoimmune disease in mice which might rule out its use in treating CFS.
Its not known if raltegravir is active against XMRV, the retrovirus associated with chronic fatigue syndrome. Given the similarity between the genomes of MLV and XMRV it seems likely that the drug will inhibit the virus. If the ability of raltegravir to treat CFS is tested in clinical trials, it will be important to carefully monitor treated patients for signs of autoimmunity. CFS has an autoimmune component which could worsen with raltegrivir treatment.

An obvious question is whether raltegrivir induces autoimmunity in AIDS patients. Im not aware of any such reports, which is probably not surprising given the fact that HIV-1 infection leads to immunosuppression.

CFS sufferers should not despair: other antiretroviral drugs, including chain terminators such as AZT, do not allow the accumulation of unintegrated viral DNA. These compounds might be useful for treating the disease.
This guy has been playing with the XMRV virus for a while now in the lab. There are a couple of fun podcast about XMRV as well. I have the site on my RSS list.
 
K

_Kim_

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Love that Blog

George, thanks for posting the latest virology blog. I arrived there weeks ago reading about XMRV and found myself wandering into other topics - all so fascinating and well-written. This latest blog shows that he really is interested and thinking about XMRV and it's connection to CFS patients. I get just as much out of some of the comments as I do from the blog itself. Good geek reading!
 
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cold_taste_of_tears

Guest
Thanks for posting this.

A psychiatrist once told me I'd never be able to cope with life, even if I did recover.

I wonder if one does recover, if that has to be the case?!

It's good to dream, thanks for some positive ideas. :)
 
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Thanks for posting this.

A psychiatrist once told me I'd never be able to cope with life, even if I did recover.

I wonder if one does recover, if that has to be the case?!

It's good to dream, thanks for some positive ideas. :)
WOW that guy is in the wrong line of work. what a terrible thing to say in his position
 

annunziata

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Thanks for posting this.

A psychiatrist once told me I'd never be able to cope with life, even if I did recover.

I wonder if one does recover, if that has to be the case?!

It's good to dream, thanks for some positive ideas. :)
I'm appalled that a psychiatrist said that to you. You have coped heroically with a hellish disease and all it brings with it.
 

liverock

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Thanks for posting this.

A psychiatrist once told me I'd never be able to cope with life, even if I did recover.

I wonder if one does recover, if that has to be the case?!

It's good to dream, thanks for some positive ideas. :)
Make an appointment to see this psychiatrist again ASP. When he leaves the room for any reason spit in his cup of coffee. XMRV could be contagious and all we need is a few psychiatrists going down with this disease to blow all these stupid peoples theories out of the water and know what its really like to suffer.

Better still pee in the cup as well. Even if XMRV is not contagious you'll feel better. :)
 

fresh_eyes

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Two blogs on raltegravir

http://cfidsresearch.blogspot.com/2009/11/raltegravir-is-likely-effective-against.html

Raltegravir (Trade name Isentress), is a drug that inhibits retroviral integrases. In the article Beck et. al "Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir", the author states in Proceedings of The National Academy of Science that "the activity profile of raltegravir on the replication or murine leukemia virus is similar to that for HIV, and that the drug specifically affects autoimmune disease in mice, in which endogenous retroelements are suspected to play a role." Both parts of this statement are highly significant.

The inhibition of Murine Leukemia Virus Integrase, which is almost identical to XMRV integrase, is not that surprising after all. The catalytic sites of retroviral sequences have a series of conserved residues which are essential for activity, meaning that this enzyme is probably the best therapeutic target for XMRV. Integrase inhibitors alone could work very well as monotherapy, and Dr. Mikovits stated that HAART is probably not necessary. Because XMRV is a slow replicating virus, the chances of the virus becoming refractory to inhibitors of retroviral integrase are slim, as compared to HIV. The drug raltegravir has a much, much better safety profile than NNRT's, which inhibit reverse transcriptase - which have side effects such as lipodystrophy, and the possibility of liver damage. The downside is: Isentress is very expensive, costing about $1100 a month, something insurers definitely will frown upon - which may lead to some of them requiring a trial course of an NNRT before covering an integrase inhibitor.

The second part, where raltegravir induced lupus in genetically succeptible mice also could have a very profound effect in treating autoimmune diseases in the future. What is significant is that Lupus favors one arm of the immune system, while Rheumatoid Arthritis, Psoriasis, Ankylosing Spondylitis, Crohn's disease favor the opposite arm. This is significant, in that XMRV could induce the translation of endogenous retroelements - of which there are over 7,000 on the human genome -which human cells do not have the machinery to transform them into proteins (no human promoter can activate them), leading to the expression of foreign proteins on the surface of human cells, which makes the immune system recognize these cells as foreign. It also lends credibility to the fact that Fibromyalgia is often co-morbid with disorders such as Rheumatoid Arthritis. It also lends credence that Lupus is the polar opposite of RA, AS, Psoriasis - leading me to theorize that an antiretroviral could bring about a clinical remission in AS, RA, PsA patients - the same groups that currently benefit from anti-TNF therapy, but could exacerbate lupus. So Lupus might be a true autoimmune disease, while on the opposite side a viral mediated quasi-autoimmune state exists.

**It is also noted that Echinacea extracts have been reported to produce lupus flares.

G.B. Beck-Engeser, D. Eilat, T. Harrer, H.-M. Jack, M. Wabl (2009). Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir Proceedings of the National Academy of Sciences : 10.1073/pnas.0908074106
 

SeaShel

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Thanks yet again fresh_eyes.

Maybe this guy should come back and apply for a position at WPI?!

Happy Thanksgiving -

Shelley
 

Daisymay

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Thanks

Thanks v much yes this is an excellent blog, lots of good stuff looking back in time, and he does seem to have good credentials.
 
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Thanks for posting this.

A psychiatrist once told me I'd never be able to cope with life, even if I did recover.

I wonder if one does recover, if that has to be the case?!

It's good to dream, thanks for some positive ideas. :)
I know this is off the virus topic, but I felt compelled to respond for professional reasons.

I'm a psychologist, and one with CFS/ME. Having observed a lot of people coping with illness, and a lot of people recovering from illnesses and returning to "normal," I can tell you that observations of a person's behavior and psyche while they are ill is a poor predictor of their coping capacity in normal, well life. It's "reasoning backwards" quite inappropriately. Others have already commented on the poor professional conduct of having mad such a comment at all.

What I would point out, and as a professional mind you, is that anyone who has been sick a long time with an illness that effects such things as mood, motivation, cognitive capacity and such, has absolutely no idea about who or how they would actually be without the pall of illness. There is no way to sort out how much of ones symptoms like anxiety, depression, low motivation, poor thinking, etc, is a function of the illness versus baseline. However, it's an open question that I would dearly hope you have your own damned chance to discover for yourself!

A similar attribution difficulty often happens the other way: well people reason that they would manage illness much better than the ill person they are observing, and so are disparaging of the ill for their "weakness of character." I once had a client who was suffering from terrible PTSD after his wife's death tell me how disparaging of the returning Vietnam soldiers he had once been. Now being there himself he was embarrassed at his former view. Your psychiatrist was similarly guilty of an "attribution bias" well known in Social Psychology: Observers tend to attribute internal personal causes to behavior they are observing, while actors are more likely to attribute external causes to features of their own behavior.

On the other hand, acting like a jerk, as your psychiatrist was, certainly doesn't tend to improve with illness. Once a jerk... you know. None-the-less, life's circumstances can even give us jerks insights, as I noted with my former client and as I would have to confess to myself relating to a number of poorly considered views! So, perhaps I would be more sanguine to your report of this awful comment if I was not irritable and cranky from CFS/ME. Or maybe I'm the grouch by nature that my kids tell me I am! Wouldn't I like to find out!
 

gracenote

All shall be well . . .
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virology, psychiatry

Thanks for posting this, Dan. Interesting blog and comments afterwards.

I read this right after reading an article by Simon Wessley posted on a different thread. What a difference when you switch from an article from psychiatry to one from virology. I must say, I like the virology one better. :) One doesn't need to feel so scrinchy.
 
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Thanks for posting this, Dan. Interesting blog and comments afterwards.

I read this right after reading an article by Simon Wessley posted on a different thread. What a difference when you switch from an article from psychiatry to one from virology. I must say, I like the virology one better. :) One doesn't need to feel so scrinchy.
Thank you Gracenote. I now see that Timothy Luckett has commented there as well as written about Raltegravir in a recent blog. As far as psychiatric manifestations of CFS...I hope the doctor you note is aggressive in pointing out the well known psychological effects of being chronically affected by an illness which originates outside the mind...as well as the well known effects of the immune components on the brain and therefore affect. :)
 

gracenote

All shall be well . . .
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nope

I hope the doctor you note is aggressive in pointing out the well known psychological effects of being chronically affected by an illness which originates outside the mind...as well as the well known effects of the immune components on the brain and therefore affect. :)
Nope, not at all. But that discussion is happening on another thread and it would be best to leave it over there.

This one quote from Vincent Racaniello is enough for me today.

CFS sufferers should not despair . . .