Eradicating HMRV (or whatever they name it next)

[urbantravels]

My search for open clinical trials on CFS has these two for Rituximab:

Recruiting, http://clinicaltrials.gov/ct2/show/NCT01156922?recr=Open&cond="Fatigue+Syndrome,+Chronic"&rank=2
B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome

Not yet recruiting, http://clinicaltrials.gov/ct2/show/NCT01156909?recr=Open&cond="Fatigue+Syndrome,+Chronic"&rank=1
B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome

Apparently based on this initial study:

http://www.biomedcentral.com/1471-2377/9/28
Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

 

[mojoey]

Why wouldn't a vaccine help if you've already been exposed? Isn't a HIV vaccine considered the holy grail of HIV treatment, not only HIV prevention, especially given the recent finding that we have antibodies that can destroy 90% of all known HIV strains?

If there is any way we can inject MLV/XMRV-specific DNA or proteins we could elicit an immune response to the pathogen. In theory it works. In practice, we would have to make sure the injected virus or parts of virus are inert and that the injected substances WOULD actually elicit an immune response.

The following are the challenges (per wikipedia) with HIV vaccine:

Classic vaccines mimic natural immunity against reinfection generally seen in individuals recovered from infection; there are almost no recovered AIDS patients.

Most vaccines protect against disease, not against infection; HIV infection may remain latent for long periods before causing AIDS.

Most effective vaccines are whole-killed or live-attenuated organisms; killed HIV-1 does not retain antigenicity and the use of a live retrovirus vaccine raises safety issues.

Most vaccines protect against infections that are infrequently encountered; HIV may be encountered daily by individuals at high risk.

Most vaccines protect against infections through mucosal surfaces of the respiratory or gastrointestinal tract; the great majority of HIV infection is through the genital tract.

MLV counterpoints:

Unlike HIV, MLV may not be a fatal infection in vast majority of cases.

Vaccine wouldn't in theory wipe out the reservoirs, but could remove the disease, which is maybe all we can hope for before gene therapy.

Whole-killed organism has been used safely in FeLV and is effective, so that may be feasible with MLV.

Transmission and true incidence is still unknown.

Unlike HIV, MLV seems to have a much lower mutation rate, so that increases the chance of our bodies producing reliable neutralising antibodies, which is one of the major challenges (unlisted above) of producing HIV vaccine

 

[leela]

My understanding of vaccination is that it introduces dead (sometimes live) virus into the system to force it to create antibodies.
If you already are infected, you are either already producing antibodies, or somehow unable to. Here I am mebbe talking out me arse again...
EIther way, any time I've been vaccinated in the past I've gotten really sick. Thus I avoid doing it now....

 

[mojoey]

The presence of antibodies doesn't mean our immunity toward that pathogen is optimal. The goal of vaccination is not only to introduce immunity but to improve immunity. Our immune system is not perfectly efficient; a vaccine can produce a targeted response. At any given point in time, our bodies are fighting multiple infections, and in the case of ME/CFS is responding pointlessly to chemicals, foods, toxins, allergens etc. Our immune system is utterly dysfunctional and th1/th2 imbalanced despite the presence of antibodies, so the introduction of a vaccine would take away the pointless distractions, so to speak, and turn a shotgun into a laser.

 

[leela]

How would a vaccine specific to one pathogen take away the pointless distractions? I don't get it.
I would think adding more antibodies would only add to the confused muddle, especially if, as an already-infected person, you are already making,
or not recognizing, said antibodies. This is of course all pure conjecture on my part based on a reeaaally elemental understanding of the vaccine
process.
I have see signs at my local drug store for "shingles" vaccine--which would indicate that vaccines work on pre-infected individuals, since anyone who had chicken
"pops" as a kid has latent VZV. Perhaps that's the distinction? A vaccine works for a latent infection, but maybe not an active one? I dunno.

 

[mojoey]

Like you said earlier, you're adding dead virus to the system, not antibodies. I also can't understand or explain exactly how this stimulates the immune system to recognize the agent as foreign and destroy it, but it seems to work in many infectious illnesses outside of HIV (presumably due to HIV's accelerated mutation rate and the above concerns).

Earlier I said vaccines can be used to introduce immunity and to improve immunity. In other words, it can both be preventative and therapeutic. In the latter case for ME/CFS, assuming we have the appropriate antibodies to the virus already, we're just redirecting all of our immunity to the pathogen.

To give you an example of how "distractions" make a huge difference in the immune response, consider this:

When two or more vaccines are mixed together in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components. - http://en.wikipedia.org/wiki/Vaccine#Developing_immunity

Targeting one thing at a time is very powerful. Treating two things at a time is much less so. Treating the 80+ infections ME/CFS patients have in their bodies plus the hundreds of chemicals, toxins, foods, etc? Well you get the drift.

 

[Daffodil]

m0joey..is there any disease where a vaccine is given after infection?

 

[mojoey]

HPV: http://www.aidsmeds.com/articles/hiv_hpv_vaccine_1667_17582.shtml

hepatitis C: http://www.hivandhepatitis.com/2010_conference/easl/docs/0427_2010_b.html

Both contain protein segments of the virus.

Cancer: http://www.rsc.org/chemistryworld/News/2008/April/17040801.asp
http://www.boston.com/news/health/blog/2010/04/fda_approves_th.html

There are also trials going on with therapeutic hepatitis B vaccines.

 

[mojoey]

Leela--A short discussion on administering monoclonal antibodies (like rituximab) versus therapeutic vaccines:http://www.nature.com/nrd/journal/v3/n1/full/nrd1284.html

Therapeutic vaccination for chronic diseases: a new class of drugs in sight

Martin F. Bachmann & Mark R. Dyer

Abstract
The induction of antibodies by prophylactic vaccination against infectious diseases has been the most effective medical intervention in human history. More recently, monoclonal antibodies specific for host proteins have proven to be highly effective for the treatment of acute and chronic diseases. However, the costs of protein therapies and their inconvenience for the patient are major obstacles for their wide-spread use.

We suggest that the movement from the passive administration of monoclonal antibodies to active vaccination against self-molecules could be the next logical step in drug development, providing affordable medicines and broader patient acceptance and compliance.

 

[Cloud]

Being told that my xmrv Serology results (pending) will have a significant contribution to designing my treatment plan, I have wondered if it will have to do with an intervention designed at alerting my immune system of the xmrv presence....such as a vaccine. If so, for me it would take some serious convincing of the safety and efficacy of this intervention since my onset was originally triggered by a Vaccine (Hep B). Aside from my onset history, the idea of a vaccine (or any other agent causing immune insult) for a pre-existing infection in a person with a severely compromised Immune system, sounds like a huge gamble....but I'm listening.

I like what Acer said....."So I guess the question is... if you can keep away from further immune insults that will increase replication again substantially (ie infection, mold, significant stress (cortisol), androgen spikes, etc..) will the virus eventually completely clear from the organ/tissue reservoirs - or, will it always come roaring back given the right stimulation?"

 

[Cloud]

I've been aware of the risk of viral reactivation in stem cell transplant (even from one's own bone marrow), but the above is also a very interesting theory, mojoey.

This virus could explain SO much about what goes wrong in us....

For instance I recently started on micro-dose hydrocortisone to try and kick-start my non-functional adrenals, and instantly had viral reactivation (haven't tested for X/P yet, but recognized the EBV/HSV reactivation signs.) I am beginning to suspect that the adrenal shutdown, like so many of our symptoms, is actually a compensation the body makes to keep the viruses under control. It would seem certain systems are down-regulated deliberately by the body in order to lower replication of viral pathogens. This could be an argument that there's no point in treating most of the systemic dysfunctions until XMRV is under control.

Dr Cheney has been saying something very similar for many years. Based on my own experiences, I believe this is correct.


Also...on the LDN, I would have to disagree that it can't backfire. Nothing makes me more ill than LDN. I know several pwc's who were thrown into horrible and long lasting relapses from taking LDN. But, I also know some who have good results. It seems that pwc's react full on good or bad to LDN...very few have benign responses.....and that can be quite diagnostic.

Great thread Joey!

 

[leela]

It is also interesting that a couple of the studies that recently came out indicate some sort of cooperation between EBV,HSVs, and MLVs.
This goes a long way in explaining why something like 90% of people have EBV but never get sick from it, and something like 1 in 3 have HSV or some such and also rarely suffer. If X/P is playing hopscotch with them, that might explain why we are almost constantly reactivated.

And Cloud, I understand your cautious approach to the vaccine idea. Be it a chemo drug or a vaccine, I'm not so excited about any more insults to my immune system.

Targeting one thing at a time is very powerful. Treating two things at a time is much less so. Treating the 80+ infections ME/CFS patients have in their bodies plus the hundreds of chemicals, toxins, foods, etc? Well you get the drift.

And Mojoey, I am clear about the "distractions" in our riddled systems. What I am still not clear on, is how introducing virus particles (I misspoke when I said antibodies) can target just one thing in the whole sea of stuff the body is trying to fight. Presumably we are already producing antibodies to ALL these little piggies,
and somehow not always able to use them successfully. How does a vaccine redirect the immune system to that ONE pathogen? Is it a question of the suddenness of the introduction that just gets the immune system's attention? The quantity of virus particles introduced into a blood stream that has already packed away virus from blood to tissue stores?
I just don't get it.

 

[mojoey]

Hey Leela,

I don't really get it either. If it's any consolation, i'm not really sure researchers studying vaccination truly get it either

There's a lot we don't understand about how the immune system works, but in the case of an acute exposure, much of the immune system is allocated to recognizing and destroying the pathogen. When I catch bugs these days, my immune response seems to shift a lot of my symptoms. This acute exposure is simulated by a vaccine. In the case of therapeutic vaccination for ME/CFS I conceptualize it as re-focusing the immune system. It may very well take repeated vaccinations to achieve this, or it may very well be that vaccination doesn't do much in the case of severe underlying immune dysfunction, but I see that as equivalent to surrendering our immune system's evolution to the pathogen's evasive evolution. I guess we'll just have to wait and see.

 

[mojoey]

Thanks Cloud!

I do share your concern about vaccination as my illness was precipitated by Hep B vaccine too, but I also share your wait-and-see mode. I think an outright dismissal of vaccination is not healthy, especially because they (in theory) work more far more in concert with our own bodies than ARVs. I think what we're seeing here is that there really doesn't exist a way to deal with an acute retroviral syndrome that isn't a gamble. Even with gene therapy tweaked retroviral vectors are often used. I expect that the same concerns we're seeing now with vaccination may eventually be seen with gene therapy.

 

[mojoey]

Someone posted a comment on Dr D-J's latest blog about an anti-TSG101 peptide http://treatingxmrv.blogspot.com/2010/09/snydermanmikovits-poster-presentation.html#comments

This is very exciting! Has anyone heard more about this?

 

[mojoey]

Ah here we go:
TSG101 exposure on the surface of HIV-1 infected cells:
implications for monoclonal antibody therapy for HIV/AIDS http://www.functional-genetics.com/pubs/2010_Diaz_et_al_AJTR1007002.pdf

Specifically, viruses
that encode for proteins with amino acid sequences
encoding for late domain motifs, most
notably HIV and Ebola viruses, bind TSG101
and that this interaction is necessary for progeny
virus release from the cell membrane. [17-
24]. In the case of HIV, the late domain motif is
part of the p6Gag protein, which binds TSG101
and facilitates the budding and release of mature virions

In summary, the surface exposure of TSG101
on infected cells could provide an important
new tool to combat HIV/AIDS. Our present studies
indicate that this unique change can facilitate
monoclonal antibody-based elimination of
infected cells via effector cell mechanisms such
as ADCC. This approach appears to be broadly
relevant to all variants of HIV and SIV tested to
date, which raises an intriguing possibility that
TSG101 antibodies, such as CB8-2, could provide
a broad-spectrum means to control HIV
infection.

From their NIH abstract:

We will present promising preliminary evidence demonstrating that XMRV infection in particular is associated with surface exposure of TSG101.

If you look at Functional Genetics Inc's product pipeline, the anti-TSG101 monoclonal antibody in the works is FGI-101-1A6. It is listed as the broadest spectrum antiviral monoclonal antibody, as well as the the monoclonal antibody for prostate cancer (XMRV anyone???)

Functional Genetics, Inc. filed its first IND in 1Q10 and two additional INDs are on track for submission in 3Q10 and 1Q11.

 

[Otis]

Facinating. I haven't read much of the paper yet. Is the idea of loooking at "hijacked" host-encoded molecules as a means of controlling viruses relativly new? Are we possibly on to a new class of drugs here?

 

[Daffodil]

cytolin begins human trials:

http://www.medicalnewstoday.com/articles/176620.php

 

[mojoey]

I don't think cytolin is relevant to MLVs because it works by theoretically inhibiting CD8 CTL killing of CD4 cells, thereby boosting the immune system's chance of controlling the virus. CD4 cells are not killed off in ME/CFS.

 

[mojoey]

Hey Otis,

I don't know if this will launch a new class of drugs unless it's found that all hijacked molecules are subsequently expressed as surface proteins, and if so, if they're only uniquely expressed on the infected cells. Monoclonal antibodies only act on surface proteins.