Re: Cancer medicine used on CFS patients is making headlines in Norway

October 19, 2011

Proposed mechanism for Rituximab in ME/CFS

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.

It will probably come as no surprise to those familiar with my history here

that I will propose a mechanism that fits with the GD-MCB hypothesis for the

pathophysiology of ME/CFS.

O.K., here it goes:

Based on the body of immunological studies that have been done in ME/CFS

over quite a few years, we know that the immune system is dysfunctional in this

disorder. In particular, it has a pronounced shift to the Th2 type of response,

away from cell-mediated immunity.

The NK cells and the cytotoxic (CD8) killer-T cells are ineffective, partly

because they are unable to produce enough perforin to punch holes in cells that

are infected with viruses. Since this is the main mechanism normally used to

knock out viral infections, these infections cannot be knocked out.

The immune system is forced to use its fall-back mechanisms, which are the

humoral immune response (antibodies produced in Th2 by the B cells, which become

plasma cells, and the interferon-induced mechanisms, including RNase-L).

These are less effective and are not able to completely knock out viral

infections (The cell-mediated cavalry never arrives). This is the reason for the

ongoing guerrilla war in the person's body, with both the reactivated viruses

which have been in the body in the latent state, and with new ones that come

along and infect the person after the onset of ME/CFS

As has been noted, the B cells do produce proinflammatory cytokines, which

of course promote inflammation. Because most PWCs also have a dysfunctional HPA

axis, cortisol tends to be low, and the inflammation is allowed to intensify to

a higher level than normal.

Note that one of the main features of inflammation is oxidative stress,

because cells of the immune system produce oxidizing species to attack the

body's enemies. Oxidative stress is well-documented in ME/CFS, with perhaps 20

published papers reporting evidence of it now.

And those familiar with the body's antioxidant system will know that when a

state of oxidative stress is present, the antioxidant system is losing the

battle between oxidants and antioxidants.

Those familiar will also know that glutathione is the basis of the

antioxidant enzyme system in the body. So now we come to realize that in the

subset of PWMEs/PWCs in whose bodies infection is a major aspect of their

illness, we can expect that a major part of the oxidative stress, and hence a

major part of the demand on glutathione, will be due to inflammation, which is

being stimulated by the B cells in the overactive Th2 immune response.

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.

I would welcome any criticisms of this proposed mechanism. As far as I can

tell, everything fits together well.

If anyone wants to get more information on the GD-MCB hypothesis, I

recommend watching the video at

http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/$%7Bweburl%\

7D

The slides from the talk are available there too, if you don't want to hang

in for the whole 3-plus hours.

Best regards,

Rich

>

http://www.tv2.no/nyheter/innenriks/helse/norsk-gjennombrudd-kan-loese-megaaten-\

3519588.html

>

> Put in google translate

>

> P.

>

October 21, 2011

I got tested for the Epstein Barr Virus, Cytomegovirus and another one.

The viral load was very low, but I'm still tired. So would Rituximab

work in my case. Does the viral load have to be high?

On 10/19/2011 8:22 PM, rvankonynen wrote:

> Proposed mechanism for Rituximab in ME/CFS

>

> 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.

>

> It will probably come as no surprise to those familiar with my history

here that I will propose a mechanism that fits with the GD-MCB hypothesis for

the pathophysiology of ME/CFS.

>

> O.K., here it goes:

>

> Based on the body of immunological studies that have been done in ME/CFS

over quite a few years, we know that the immune system is dysfunctional in this

disorder. In particular, it has a pronounced shift to the Th2 type of response,

away from cell-mediated immunity.

>

> The NK cells and the cytotoxic (CD8) killer-T cells are ineffective,

partly because they are unable to produce enough perforin to punch holes in

cells that are infected with viruses. Since this is the main mechanism normally

used to knock out viral infections, these infections cannot be knocked out.

>

> The immune system is forced to use its fall-back mechanisms, which are

the humoral immune response (antibodies produced in Th2 by the B cells, which

become plasma cells, and the interferon-induced mechanisms, including RNase-L).

>

> These are less effective and are not able to completely knock out viral

infections (The cell-mediated cavalry never arrives). This is the reason for the

ongoing guerrilla war in the person's body, with both the reactivated viruses

which have been in the body in the latent state, and with new ones that come

along and infect the person after the onset of ME/CFS

>

> As has been noted, the B cells do produce proinflammatory cytokines,

which of course promote inflammation. Because most PWCs also have a

dysfunctional HPA axis, cortisol tends to be low, and the inflammation is

allowed to intensify to a higher level than normal.

>

> Note that one of the main features of inflammation is oxidative stress,

because cells of the immune system produce oxidizing species to attack the

body's enemies. Oxidative stress is well-documented in ME/CFS, with perhaps 20

published papers reporting evidence of it now.

>

> And those familiar with the body's antioxidant system will know that when

a state of oxidative stress is present, the antioxidant system is losing the

battle between oxidants and antioxidants.

>

> Those familiar will also know that glutathione is the basis of the

antioxidant enzyme system in the body. So now we come to realize that in the

subset of PWMEs/PWCs in whose bodies infection is a major aspect of their

illness, we can expect that a major part of the oxidative stress, and hence a

major part of the demand on glutathione, will be due to inflammation, which is

being stimulated by the B cells in the overactive Th2 immune response.

>

> 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