Astounding Norwegian research breakthrough with Rituximab can solve CFS mystery!!!

[justy]

Thank you so much Rich for taking the time to explain the situation as you see it so clearly. Like you i hope that the MCBH is looked into in more detail. I remember Dr Mikovits saying something about methylation treatment in one of her talks as being useful so it seems that some researchers are taking it seriously.

My first thought after seeing the rituximab talk was " how can i get to Norway for a trial" but my second thought was "hmm, risk death and deplete an important aspect of my immune system" not for me for now but i am very encouraged by the talk that they are now doing a further larger trial (was due to start Oct 2011) and they are working very hard to see what else is going on and to work out why the rituximab is helping.
It will be interesting to see if this study gets as much attention in the Lancet as the death threats story.
All the best, Justy.

Hi, justy.

Thanks for hanging in there for my whole talk! I appreciate knowing what the researches said about the patient on placebo who recovered. All of us suffer from lack of an agreed-upon, solid case definition that is tight enough to give a very homogeneous cohort. It is hard to believe that a person who is seriously ill from ME/CFS could be cured by salt water!

With regard to IV infusion of glutathione, this has been done and is being done by quite a few practitioners. The general experience is that in most cases it brings temporary relief of symptoms (for about a day or two), but in a subset it actually makes the symptom picture worse. When glutathione is given by I.V., about 80% is taken out of the blood by the kidneys. It is initially broken down, and then some is reformed. Some cysteine is put back into the blood. About 10% is taken by the lungs. The rest goes to a variety of tissues. The problem with I.V. application is that it is apparently not able to raise the glutathione level inside the cells very much, in general. Probably the intracellular levels are raised more by use of liposomal glutathione, or possibly the acetylglutathione that is now being offered. But I think it is still likely that the vicious circle mechanism will prevail unless glutathione comes up a lot, on a sustained basis, and lifting the partial methylation cycle block is the only way I have found that will do that on a more permanent basis. But perhaps in the two patients in this study who recovered after Rituximab treatment, just lowering the inflammation was enough to break the vicious cycle, so that glutathione came up enough to restore the B12 function to normal and lift the partial methylation cycle block.

As you know, the methylation treatment alone has not brought total recovery to very many PWMEs/PWCs, though it brings significant improvement to most. One of the possible reasons why it has not brought complete recovery in many of the cases may be that there is some condition in the body that is still placing a big demand on glutathione, and just lifting the partial methylation cycle block is not able to overcome it. Inflammation-related oxidative stress seems like one good possibility. If Rituximab lowers the oxidative stress, at least temporarily, this might be enough to help break the vicious circle. Perhaps the methylation treatment combined with one course of rituximab would push more people into recovery. This is just speculation at this point. It does seem to be true that the few people who have recovered apparently completely after the methylation treatment was given had had other types of treatment before that, some of them directed at knocking down infectious diseases, and hence, inflammation. Maybe that's how all of this fits together. Note also that there were some people in the Rituximab study who were not helped by the treatment. Perhaps the dominant glutathione demand in these people was due to toxins rather than to infections. If this was the case, knocking out the B cells would not have lowered the demand on glutathione, and that could explain why there was no improvement. There are many factors that can place demands on glutathione, and not everyone with ME/CFS shares the same ones.

I'm hopeful that as time goes on more researchers will begin to believe that glutathione is an important actor in this drama, and will begin measuring it in an accurate way. I think that could help to pull all of this together.

Thanks for your comments.

Best regards,

Rich

 

[fla]

Richvank, according to your theory can you perform a thought experiment of giving Rituximab to autism patients?

 

[kurt]

........and the consensus of those that understand this stuff is what?

What do I say to my partner? Is this a major step?

I do not speak "medical" - I'm an activist (I used to be known as a 'carer' - prefer the new label) and do not pretend to comprehend research papers - although I can get the drift, can anyone summarise the findings for me?

Go Norway.

What has happened: Thanks to the Norwegian study we know that reducing the humoral immune response (lowering B cell activity) reduced ME/CFS symptoms in 2/3 of patients in one study.

Why does this drug help? There have already been at least four theories proposed here: 1) This shows ME/CFS is an autoimmune disorder, or a disease with autoimmune elements, 2) This study supports the idea that B-cells are involved in ME/CFS (such as an HGRV, or perhaps some unknown pathogen that causes over-expression of the B-cells), 3) the experiment lifted oxidative stress from the over-active humoral immune response present in ME/CFS and thus raised glutathione levels, which has been correlated with ME/CFS symptom improvement, and 4) by reducing B cell activity, the activity of EBV or CMV might have been reduced, as they can inhabit B cells.

There might be other explanations, there is some disagreement over the mechanism of Rituximab in cancer, so this is just a starting point for further research. But what a great study!

 

[Dreambirdie]

My first thought after seeing the rituximab talk was " how can i get to Norway for a trial" but my second thought was "hmm, risk death and deplete an important aspect of my immune system" not for me for now but i am very encouraged by the talk that they are now doing a further larger trial (was due to start Oct 2011) and they are working very hard to see what else is going on and to work out why the rituximab is helping.
It will be interesting to see if this study gets as much attention in the Lancet as the death threats story.
All the best, Justy.

Hi Justy--

Your second thought was my first thought. I am glad to see the progress, but I know I would NOT be able to tolerate a drug like this. When I read the adverse effects for Rituximab, it gave me a bit of the creeps.

Serious adverse events, which can cause death and disability, include:
Severe infusion reactions
Cardiac arrest
Tumor lysis syndrome, causing acute renal failure
Infections
Hepatitis B reactivation
Other viral infections
Progressive multifocal leukoencephalopathy (PML)
Immune toxicity, with depletion of B cells in 70% to 80% of lymphoma patients
Pulmonary toxicity

I hope they learn WHY the drug is helping and come up with less toxic alternatives. For now, I'm sticking to methylation and TCM.

 

[max]

Hi Kurt

Many thanks

 

[Sushi]

Hi, all.

I think this is a very interesting development, and I want to suggest what I think is going on when Rituximab is used to treat ME/CFS....

O.K., so now we put in Rituximab, which kills the B cells. What happens?

Well, the inflammatory cytokines drop down, as does inflammation. This lowers the oxidative stress, taking a big demand off glutathione, which is then able to rise to at least some degree.

Aficionados of the GD-MCB hypothesis will immediately suspect that a big part of the symptomatology of ME/CFS will diminish, since the causes of a large fraction, perhaps the majority, of ME/CFS symptoms can be traced directly to the depletion of glutathione.

So voila! The patient feels better, until her/his B cells grow back, and the whole process repeats itself, making her/him miserable again. So we hit the patient with another dose of Rituximab, and she/he bounces back up, and so on. If we do succeed in permanently devastating the B cells, what happens in the longer term? Certainly they were there for a purpose. Will the body be adequately defended against its enemies in the future? I think that's a big question.

The main point I want to make is that this treatment, like many others that have been used or proposed for ME/CFS, addresses a down-stream issue in the pathophysiology, and does not get to the root of the problem, which I believe (and have evidence to support this belief) is a vicious circle mechanism that includes glutathione depletion, a functional deficiency of vitamin B12, a partial block of methionine synthase in the methylation cycle, and draining of folates from the cells. So far, the only way it seems to be possible to break this vicious cycle is to lift the partial block in the methylation cycle with appropriate treatment that includes simultaneous use of active forms of folate and high dosage of forms of vitamin B12. Among other effects, this should rebalance the immune system, so that the B cells as well as the other components of the immune system will return to their normal functions. I do need to add that some other things will likely need to be done as well to help this process along, and which things will depend on the details of each case. But lifting the partial methylation cycle block is the fundamental thing that needs to be done...

.

Best regards,

Rich

Hi Rich,

Please indulge me in asking what may well be a naive question. First also, excuse me for not quoting you in entirety as I just wanted to address a couple of ideas. The methyaltion theory does seem to fit here.

In my limited understanding Rituximab is fairly indiscriminate in killing B cells, and, as you point out, in most cases symptoms reappeared when the B cell population regenerated.

As you know, I and others are taking GcMAF which also seems to kill (or inactivate? excuse my lack of science) B cells, but only those infected with "something." When our B cell population begins to return to normal, we start feeling better, rather than worse. Which maybe points to idea that killing the infected cells and thus the infection, might be a better strategy than just reducing the B cell population and not targeting whatever it is that is messing with the B cells.

I'd really appreciate your scientific "take" on this idea. It is not coming from a science background, but a "scratching my head" and wondering what is happening here scenario.

Thanks!
Sushi

 

[fawkes]

It could also be hitting EBV activation in B cells; those are after all the cells that EBV hangs out it. If Rituximab is knocking the B cells down it could also be reducing EBV cell activation.

Is it not also hypothesized that EBV may reside in basal or dorsal ganglia cells? Would rituximab reach these? Is it the case that most antivirals discussed in that connection (valganciclovir for one) hit only the blood cells (B cells in particular)? Which, between antivirals or rituximab, would have a better of reaching the ganglia/spinal cord? Anyone know?

 

[Kati]

Hi Justy--

Your second thought was my first thought. I am glad to see the progress, but I know I would NOT be able to tolerate a drug like this. When I read the adverse effects for Rituximab, it gave me a bit of the creeps.

Serious adverse events, which can cause death and disability, include:

Again I have given Rituximab hundreds of times while working as a nurse with cancer patients.
Severe infusion reactions
Cardiac arrest
Tumor lysis syndrome, causing acute renal failure
Infections
Hepatitis B reactivation
Other viral infections
Progressive multifocal leukoencephalopathy (PML)
Immune toxicity, with depletion of B cells in 70% to 80% of lymphoma patients
Pulmonary toxicity

I hope they learn WHY the drug is helping and come up with less toxic alternatives. For now, I'm sticking to methylation and TCM.

Again I have given Rituximab hundreds of times while working as a nurse with cancer patients. I would like to share my experience and dispell some myths on Rituximab. This is in answer to Dreambirdie's post.

1) Severe infusion reactions: This is why the infusion needs to happen in a hospital, not at home, not in a doctor's office. I have had quite a few infusion reactions in my carreer, 1 which resulted to a transfer to emergency. Out of a few hundreds. The rest of them resulted on giving Benadryl and Steroids to quiet the immune system. Most patients were able to finish the infusion without further reactions. Dr Mella and Fluge mention a trial with severe ME, to do plasma exchange before attempting Rituximab, in order to reduce the risk of these reaction due to increased circulating antibodies.

2) Cardiac arrest: never seen that in the 8 years of my career in cancer nursing, not even heard of it happening. We were certainly ready to this possibility for any chemo though- with a crash cart on the ward.

3) Tumor lysis syndrome- If you don't have a tumor- it's not going to happen. This happens with patients with Burkitt's and other types of lymphomas, yet oncologists are very aware of this and treat preventively.

4) Infections- Yes this is a possibility that patients need to be aware of. When they are b-cell depleted, they need to report to the hospital when they have fevers. It didn't happen with any of the patients on the Mella/Fluge study.

5) Hep B reactivation - if you don't have Hep B- it's not going to happen. Hep B patients get Lamivudine in prevention during their chemo.

6) PML- I hear that a new drug is available for RA patients to treat this. Again this is a condition I have never seen in the cancer population.

7) Pulmonary toxicity- I have never seen it either- Pulmonary toxicity can happen more often with other chemo drugs given with RItuximab, so which one is which?

Certainly the choice to receive a drug or participate to a trial is yours and yours only. When you sign a consent for trial drug, it is the responsibility for the doctor to explain the risks, and each one of them. It can be scary but it's their job. If the benefits outweigh the risks, then people go for it. Cancer patients bravely agree to get drugs that have never been tested on humans, usually when they have ran out of options and they know that their cancer is not curable. These people have contributed to the advances of science.

With Rituximab, this is a well known drug, with well known side effects. I have litterally seen people coming back from the dead with Rituximab, and a few months later going back to work.

I would like a chance at life, and Rituximab, I feel, gives me that chance.

 

[Sing]

Thank you so much, Kati, for your information from being a cancer nurse and employing Rituximab. It gives me more confidence that, if I get the opportunity, I would try this.

 

[Dreambirdie]

There is no way I could do that drug. I have horrible drug reactions, and that one would not be an option for me.

 

[kurt]

This is just too ironic, so I have to mention:

Rituximab is a mouse/human chimaeric IgG(1)-kappa monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal B lymphocytes. Although treatment with rituximab induces lymphopenia in most patients, typically lasting about 6 months, a full recovery of B lymphocytes in the peripheral blood is usually seen 9-12 months after therapy, as CD20 is not expressed on haematopoietic stem cells. CD20 is, however, expressed on >90% of B-cell non-Hodgkin's lymphomas (NHL) and to a lesser degree on B-cell chronic lymphocytic leukaemia (CLL)
source: http://www.ncbi.nlm.nih.gov/pubmed/12662126

Seems we just can't get away from mice! Rituximab is a murine-human chimera!

 

[Guido den Broeder]

Is it not also hypothesized that EBV may reside in basal or dorsal ganglia cells? Would rituximab reach these? Is it the case that most antivirals discussed in that connection (valganciclovir for one) hit only the blood cells (B cells in particular)? Which, between antivirals or rituximab, would have a better of reaching the ganglia/spinal cord? Anyone know?

EBV that hides in in B Cells makes them immortal, thereby increasing the production of antibodies against amyloid beta. That, in turn, causes oxidative stress. This is latent, immature EBV, so destroying these cells could be effective for quite a while.

The ganglia are more likely to be infected by an enterovirus, I think. But with EBV out of the way, the immune system should be able to deal with an enteroviral infection.

Of course, there may be other concentrations of EBV, and also ME patients could have another herpes virus instead of or in addition to EBV.

 

[justinreilly]

Somehow I'm getting your comment like just ignoring woud be something new or special and unimaginable... ^^

yeah, they've ignored all the other proof, so why not this?

 

[Sing]

This is just too ironic, so I have to mention:



Seems we just can't get away from mice! Rituximab is a murine-human chimera!

Hi Kurt,

What is a murine-human chimera?

 

[alex3619]

Hi Sing, in legend a chimera is a fictional beast made up of parts of other beasts, such as lion goat or serpent. Chimeric DNA is any DNA that is made from several different species. It is genetically engineered. However this term is sometimes used to refer to people who have xenotransplantation - such as pig implants. Bye, Alex

 

[Snow Leopard]

So what auto-immune disease follows infectious outbreaks? None are acknowledged as yet. Rheumatoid arthritis, Lupus etc dont come in infective outbreaks.

There is plenty of discussion in the scientific literature about virus induced autoimmunity.

 

[ixchelkali]

I understand your desire for enthusiasm 100% too! There are a few things going on in CFS I'm vaguely hopeful about, and this is now high on that list, but it's best to remember how results like these could just be indicative of nothing.

Color me cautious, too. But then, I'm usually in the "let's wait and see what the science tells us" camp. But I don't think the results are indicative of nothing. The thing is to figure out WHAT they indicate.

Some of our long-time clinician heroes have said for a long time that it seems like the immune system gets turned on by some insult, like a viral infection, and gets stuck in the "on" position. Who knows? Maybe it's as simple as that, and using a drug that shuts down the immune system (or parts thereof) will take care of it. But personally, I'd like to have a better idea of why the immune system is turned on before I turn it off.

Somehow, the autoimmune hypothesis doesn't explain enough to me. If it's an autoimmune disease, what causes the post-exertional malaise (or PENE, or whatever you call it)? How do you explain the outbreaks? Why do people with ME/CFS have above normal levels of several viruses, like EBV and HHV6? Why is EBV often a trigger?

I just think that any valid hypothesis about this disease must explain all the elements of the disease. Too much of the ME/CFS research has been like the blind men and the elephant, with researchers shouting "Eureka!" when they've only got hold of the tail. To me, this study is just one more piece of the puzzle, and adds one more question to be answered: why do patients feel better when you zap their B-cells? But saying that it's an autoimmune disease doesn't work as a unified theory, to my way of thinking. Not yet, at least; not without more explanation and research. But maybe it will intrigue some immunologists enough to spur further research; that would be good.

 

[urbantravels]

Hey, someone changed the topic title that I created? What on earth for? The new headline isn't something I would ever say; I don't like having words put in my mouth. If the humor of the original wasn't apparent, then geez you guys, lighten up.

 

[urbantravels]

...and apparently I can't change it back either. That's just not cool.

 

[livingwithcfids]

Does anyone know how many of the patients on this cancer drug showed significant improvement? So, as you've said the new direction in which they will focus their attention will be on ME/CFIDS as an auto-immune condition with emphasis on white blood cells. I also heard the drug works best on patients who have had CFS less than 5 years. I just wish more countries would get involved.

The Norwegian doctors stumbled across this drug by accident. Someone who had both M.E and Lymphoma was given this cancer drug, and to the patients surprise, his M.E symptoms disappeared, so now these two doctors get all the credit.