Rituximab, a Possible XMRV Treatment?

Kati

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Marco it has been mentioned but that's ok- Rituximab is a good drug and I certainly hope that they get good results with it. I would not hesitate to get it if given the opportunity.
 
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I have the opportunity to get

Rituxan but am a bit hesitant.

According to my doctor there is a 3% chance of getting something called Progressive Multifocal Leukoencephalopathy (PML)

PML is a rare brain infection that usually causes death or severe disability. Patients should call their doctor right away if they notice any new or worsening medical problems, such as a new or sudden change in thinking, walking, strength, vision, or other problems that have lasted over several days. PML can occur during treatment with Rituxan or after treatment has finished.

Supposedly if you get this there's no cure and you will die within 6 months. Rituxan is made from mouse proteins. There is another drug called epratuzumab that is made from human protein (this is my understanding) According to my doctor epratuzumab has less side effects but is not yet approved by the FDA.

I think rituxan is given with methotrexate, which suppresses the immune system. I'm not sure how that would work if we have XMRV.

http://online.wsj.com/article/SB124381351149970563.html
 
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I think I would take AZT before I would take rituximab. Especially before the results of the follow up rituximab study come out (the Norwegians are now doing a placebo controlled trial on 30 patients).
 

Kati

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I think I would take AZT before I would take rituximab. Especially before the results of the follow up rituximab study come out (the Norwegians are now doing a placebo controlled trial on 30 patients).
I would tend to agree with this idea IF XMRV is +
It is not yet known if Rituximab is temporary or not- but it sounds like there has been great benefits- I would also suspect (nothing scientific) that Rituximab would help prevent B and T cell lymphoma, which is a good thing considering that CFIDS patients are at higher risk of getting it (acording to Dr Peterson)

Tough choice-
If you are paying for the drugs, money might be an issue as wel. I know Ritux is not cheap at all, don't know about AZT.
 

redo

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Rituximab and XMRV, a possible connection?

As many others I got uplifted when I saw the results from the study on the "anti-CD20 antibody" medicine "Rituximab" on the three CFS patients.

You can see the results from the study here. The further down the graph goes, the better the CFS patient is. If the graph shows "1", then that means that the patient is symptom free (yes, I know, "0" would be more logical, but that's the way they have done it).



And I find it is especially interesting in the light of the new XMRV discovery. There could be a connection.

For one we know that XMRV is a retrovirus. One of the most important mechanisms of the HIV infection is that it lowers the NK count of the CD4 cells.

The Belgian scientist De MeirLeir has found that many CFS patients have low CD57 results - it might be different causes for that - but it also might be that it's because of the XMRV. HIV makes CD4 go down, XMRV might make the CD57 count go down...

Here's a quote from the scientist who published the study (quote from lymenet):

This is from WPIs website:
" (...) The current working hypothesis is that XMRV infection of B, T, NK and other cells of the innate immune response causes the chronic inflammation and immune deficiency resulting in an inability to mount an effective immune response to opportunistic infections."

Rituximab is a B-cell depleting drug. It could be that what happens when people are treated is that it "hits" the XMRV.

Whatever reason there is for the improvement, it gives me hope to see that they improve so dramatically in the pilot study.


You can read the full text of the pilot here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711959/
 
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It could be that what happens when people are treated is that it "hits" the XMRV.
The authors propose two hypotheses. 1) CFS symptoms are caused by autoimmunity, so rituximab is having a similar mechanism of action as in rheumatoid arthritis 2) ongoing infection with a virus that infects B cells. Apparently XMRV infects B-cells so it is certainly a possibility.

asus389 said:
Personally I think an interesting drug is Bavituximab - a cousin to rituximab.
Yes, bavituximab is very fascinating! I remember someone mentioning it and it sounding very promising, but I forgot the name of it, so thanks for reminding me. :Retro smile:

Basically rituximab goes and kills all your B-cells, but bavituximab kills all your virally infected cells and tumor cells. Very exciting. There are a couple of Phase I and Phase II studies going on for cancer and hepatitis C/HIV. Maybe if it is approved for one of those we could get it off label, though it will probably be a few years at least. It's a pretty small company.
 

redo

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It might very well be that XMRV is inside B-cells, and by targeting those, you also target the XMRV. But you don't get rid of all the XMRV, so it comes back... That's one hypotesis.

The amount of B-cells and the time of their relapse did not correlate (you can read it about 2/3 down the page of the full study, link is above). But it's also very posible that the Rituximab does not only target B-cells. I wouldn't be surprised if we would see changes in HNK-cell function as well when someone gets treated. It's a new drug, and I doubt studies have been done on all of the variuos HNK-cells.
 

acer2000

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Yeah thats interesting to know about the B cell counts. I guess I just get nervous about drugs whose effects on a disease isn't 100% understood and which manupulate the immune system by reducing populations of cells. Athough since CFS isn't 100% understood I guess thats all we have. :)
 

determined

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cancer treatment

The fatigue/weakness component of my health problems improved dramatically when I underwent chemotherapy for cancer. It lasted for quite a while. I've heard this from others with CFS who have had cancer as well.
 

Kati

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The fatigue/weakness component of my health problems improved dramatically when I underwent chemotherapy for cancer. It lasted for quite a while. I've heard this from others with CFS who have had cancer as well.
Chemotherapy in general kills the fast reproducing cells including cancer cells, hair cells. blood cells. The white blood cells- including B and T cells which would be the cells of choice for XMRV are destroyed, thus creating a decrease of viral load (my hypothesis) for the virus to happily replicate. This doesn't last since your bone marrow would replace the blood cells usually within 2 or 3 weeks.

If one can overcome the nausea and vomitting usually associated with the chemotherapy, one would do fairly well.

(from your chemo nurse)
 

Jim

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i was diagnosed with xmrv, and my nk function is low. but my b-cell count has been above normal. does that sound inconsistant? i have not had my nk cell count done in years, but i don't think it was ever high.
 

Hope123

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i was diagnosed with xmrv, and my nk function is low. but my b-cell count has been above normal. does that sound inconsistant? i have not had my nk cell count done in years, but i don't think it was ever high.
The B-cells are a separate branch of the immune sytem from T-cells and NK cells so it's not inconsistent since the virus might be affecting different cells differently. I have not heard of anyone having above normal NK cell count/ function in CFS - I've heard below normal and low but normal. (Please post if you've seen otherwise.)

On the other hand, the T-cell counts and B-cell counts have been all over the place, some high, some low, some normal. Dr. Cheney, whose therapies I am skeptical of but who did make some excellent observations about CFS, wrote about T-cell counts and notes that these are likely different stages of the illness. I also think they can fluctuate depending on various things, like if herpes viruses are activated at the moment.

Also, the authors of this study are doing a trial with a larger number of people (30) and I heard from a good source that they were planning to unblind the results around this time. They are aware of the XMRV stuff going on. Hopefully, they'll be able to publish results this year. Regardless of XMRV, if this treatment is successful, it could help provide a bridge until better treatment is discovered. Like cfssince1998, I am also cautious though of immune therapies since the immune system is much more complex and interconnected than we know about.
 
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The B-cells are a separate branch of the immune sytem from T-cells and NK cells so it's not inconsistent since the virus might be affecting different cells differently. I have not heard of anyone having above normal NK cell count/ function in CFS - I've heard below normal and low but normal. (Please post if you've seen otherwise.)

On the other hand, the T-cell counts and B-cell counts have been all over the place, some high, some low, some normal. Dr. Cheney, whose therapies I am skeptical of but who did make some excellent observations about CFS, wrote about T-cell counts and notes that these are likely different stages of the illness. I also think they can fluctuate depending on various things, like if herpes viruses are activated at the moment.

Also, the authors of this study are doing a trial with a larger number of people (30) and I heard from a good source that they were planning to unblind the results around this time. They are aware of the XMRV stuff going on. Hopefully, they'll be able to publish results this year. Regardless of XMRV, if this treatment is successful, it could help provide a bridge until better treatment is discovered. Like cfssince1998, I am also cautious though of immune therapies since the immune system is much more complex and interconnected than we know about.
Dr O. Mella tell-me in Oct 09 that ther results of WPI fit well with the mecanismes behind induct of CFS. They will repeat the analysis of XMRV in their study (30 patients) will be opened from binding in the end Dec 09, but this does not mena that they can transmit the results, but analyze results and writte conclusions...
 

Advocate

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LJ001 - new antiviral claims few side effects

XMRV has a lipid envelope. The new drug LJ001 targets only enveloped viruses. The researchers claim it "does not appear to be toxic in vitro or in animals when used at effective antiviral concentrations." It appears to kill only the virus, not the cell.

If there's another discussion going on LJ001, I've missed it, so here's what I read this morning:
=============================
Researchers find 'broad spectrum' antiviral that fights multitude of viruses

Compound could be used against HIV-1, Nipah, Ebola and other deadly viruses

By Enrique Rivero February 01, 2010 Category: Health Sciences, Research *

Viruses are insidious creatures. They differ from each other in many ways,
and they can mutate at times seemingly at will, as with HIV to resist a
host of weapons fired at them.

Complicating matters further is that new viruses are constantly emerging. *

One potential weapon is a small-molecule "broad spectrum" antiviral that
will fight a host of viruses by attacking them through some feature common
to an entire class of viruses.

For example, there are two categories of viruses: lipid-enveloped and
non-enveloped.


Enveloped viruses are surrounded by a membrane that in effect serves as a
mechanism through which a virus inserts its genome into a host cell,
infecting it.

Is there something out there that might disrupt that action in as many
viruses as possible and not produce unwanted side effects? *

A group of researchers led by a team from UCLA and including others from the
University of Texas at Galveston, Harvard University, Cornell University and
the United States Army Medical Research Institute of Infectious Diseases may
have found just such a compound. *

In a proof-of-principle study published online in Proceedings of the
National Academy of Sciences, the researchers have identified an antiviral
small molecule that is effective against numerous viruses, including HIV-1,
influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses,
paramyxoviruses and flaviviruses.

These viruses cause some of the world's deadliest diseases, such as AIDS,
Nipah virus encephalitis, Ebola, hemorrhagic fever and Rift Valley fever. *

Even better, the compound a rhodanine derivative that the researchers have dubbed LJ001 could be effective against new, yet-to-be discovered enveloped viruses. * *

"Since the government has changed its priorities to support development of
broad spectrum therapeutics, more and more groups have been screening
compound libraries for antivirals that are active against multiple viruses
in a specific class," said Dr. Benhur Lee, associate professor of
microbiology, immunology and molecular genetics at the David Geffen School
of Medicine at UCLA and the primary investigator of the four-year study. *

U.S. Food and Drug Administrationapproved broad spectrum antivirals do
exist but are rare, for various reasons.

Ribavirin, for instance, affects both the virus proteins and the host cell
and is effective on only a limited number of viruses, such as respiratory
syncytial virus and Lassa fever virus.

And αinterferon, which is used against the hepatitis C virus, produces
unwanted side effects and is too expensive for widespread use. * *

But the putative mechanism for LJ001 is surprising, according to Lee, who is
also a member of the UCLA AIDS Institute. *

"We provide evidence that the small molecule binds to both cellular and
viral membranes, but its preferential ability to inactivate viral membranes
comes from its ability to exploit the biogenic reparative ability of
metabolically active cells versus static viral membranes," he said.

"That is, at antiviral concentrations, any damage it does to the cell's
membrane can be repaired, while damage done to static viral membranes, which have no inherent regenerative capacity, is permanent and irreversible." *

Lee and his collaborators developed their concept of LJ001 as interfering
only with enveloped viruses after testing 23 pathogens in cell culture.

Studies of nine of those agents including Ebola virus, Nipah virus and
Rift Valley fever virus required high- or maximum-containment facilities
and were carried out in the biosafety level 3 and 4 laboratories of the
University of Texas Medical Branch at Galveston (UTMB) and USAMRIID. *

"Once we started testing more and more, we figured out that it was only
targeting the enveloped viruses," said Alexander N. Freiberg, director of
UTMB's Robert E. Shope, M.D., Laboratory. *

The Shope BSL4 lab was also used for mouse experiments with Ebola and Rift
Valley fever virus that further confirmed the protective value of LJ001. *

While the exact mechanism of viral membrane inactivation is unknown, the
researchers are pursuing some promising leads that could answer that
question. *

Additionally, the drug does not appear to be toxic in vitro or in animals
when used at effective antiviral concentrations. *

UCLA has filed for a patent on the use of the compound. *

The study is available in Proceedings of the National Academy of Sciences at
http://www.pnas.org/content/early/2010/01/27/0909587107. *

Other authors are Mike C. Wolf, Tinghu Zhang, Zeynep Akyol-Ataman, Andrew Grock, Patrick W. Hong, Natalya F. Watson, Angela Q. Fang, Hector C. Aguilar, John P. Miller, Steven Chantasirivisal, Vanessa Fontanes, Oscar
Negrete, Robert Damoiseaux, Paul Krogstad, Asim Dasgupta, Kym F. Faull and Michael E. Jung, all of UCLA;

Alexander N. Freiberg, Sara E. Woodson and Michael R. Holbrook, of the
University of Texas at Galveston;

Jianrong Li and Sean P. Whelan, of Harvard University;

Matteo Porotto and Anne Moscona, of Cornell University; and

Anna N. Honko and Lisa E. Hensley, of the United States Army Medical Research Institute of Infectious Diseases. *

The National Institutes of Health, UCLA CFAR, the Burroughs Wellcome Fund,
the March of Dimes, the California NanoSystems Institute, a UCLA Microbial
Pathogenesis Training Grant, the Warsaw Fellowship Endowment, and a
Rheumatology Training Grant funded this research. *

The UCLA AIDS Institute, established in 1992, is a multidisciplinary think
tank drawing on the skills of top-flight researchers in the worldwide fight
against HIV and AIDS, the first cases of which were reported in 1981 by UCLA physicians.

Institute members include researchers in virology and immunology, genetics,
cancer, neurology, ophthalmology, epidemiology, social science, public
health, nursing, and disease prevention.

Their findings have led to advances in treating HIV, as well as other
diseases, such as hepatitis B and C, influenza and cancer. *

For more news, visit the UCLA Newsroom*and follow us on Twitter. *
http://newsroom.ucla.edu/portal/ucla/researchers-find-broad-spectrum-153297.
aspx *
*
 

julius

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Advocate,

Re: lj001

This is the same way that Lauric acid works. You can buy it as a supplement. It is derived from virgin coconut oil. If you take 2-4 tbsp of virgin coconut oil you get the recommended dosage of lauric acid...but it's hard to swallow that much oil without gagging.
 
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They will repeat the analysis of XMRV in their study (30 patients) will be opened from binding in the end Dec 09, but this does not mena that they can transmit the results, but analyze results and writte conclusions...
This is great news! Thank you for posting this.

This is the same way that Lauric acid works. You can buy it as a supplement. It is derived from virgin coconut oil. If you take 2-4 tbsp of virgin coconut oil you get the recommended dosage of lauric acid...but it's hard to swallow that much oil without gagging.
But does it get into the blood stream? It's never been tested in vivo. I took lauric acid (lauricidin) at very high doses for 6 months and stopped taking it because I just don't see any evidence that it can work when taken orally.