Good news! Norwegian govt funds Rituximab trial - possibly partial, amount not yet announced

[alex3619]

I have said this on two other threads, but it belongs here too. I am looking at the question as to whether methylation or oxidative stress might drive the autoimmune issues. Both deplete glutathione. B cells that are glutathione deficient will not be able to make properly folded antibodies, as glutathione is needed to make sulfide bridges. I suspect that this will often inactivate the antibody, but it may also create antibodies with low or altered specificity, resulting in attacking self proteins. This would generate a very broad range of antibody targets, degrading capacity in many systems simultaneously, while also creating issues unique to individuals. It might also fit with the failure of rituximab to induce cure in many patients, as the underlying metabolic problem is not corrected. It is a testable hypothesis. Its also means that correcting oxidative and nitrosative stress might boost rituximab results. I wonder what would happen if this approach was used and included antivirals?

Cells usually have a capacity to destroy improperly folded proteins, and antibodies are proteins. However I do not know if this is right for B cells, or if they can be deranged in other ways that do this including infection. It may be that antibody production is different, or that the machinery that destroys bad proteins is failing.

What I expect to see if this hypothesis is right is large numbers of autoantibodies of different types, with different targets, but with poor binding properties.

 

[lansbergen]

It may be that antibody production is different, or that the machinery that destroys bad proteins is failing.
.

I think it is both

 

[alex3619]

Further to my earlier post on faulty antibodies, an implication is that our antibody defence is weak, yet because of constant activation will drive us to Th2, resulting in poor defence against many pathogens. Rituximab causes a loss of B cell immune function, but given our immune function is poor under this hypothesis the loss will be substantially less than for other disorders (lymphoma, RA) than for ME. In addition over time there should be a shift back toward Th1 dominance. Rituximab plus antioxidants plus antivirals could be a cure.

Correction of methylation problems in those who have them could be mandatory to cure. I wonder if methylation issues can be shown to predominate in Rituximab non-responders?

 

[lansbergen]

In addition over time there should be a shift back toward Th1 dominance. Rituximab plus antioxidants plus antivirals could be a cure.

Levamisole can shift back to th1 and is much cheaper.

 

[alex3619]

Levamisole can shift back to th1 and is much cheaper.

But does it correct the autoantibodies, oxidative stress and abnormal cytokines? Maybe some cytokines, but I doubt much more. The point is that rituximab, under what I proposed, eliminates the problem at least temporarily, and that other factors can be treated to improve this response, perhaps all the way to cure. This is of course only speculation at this point. What we do know is that it results in substantive remission of symptoms. I don't think levamisole does that.

Furthermore it should not be forgotten that at least a subgroup of ME does not (currently) respond to Rituximab, and either this is because Rituximab is not addressing the central issue, or ME is a mix of two different cohorts, or both.

 

[Firestormm]

Quick question: does anyone know when we might be told how much money the Norwegian Govt. is putting into Trial? I don't think they have said how much but I could have forgotten. Also, the money raised by Maria's efforts do we know what % of the needed funding this represents?

Danke

 

[biophile]

Quick question: does anyone know when we might be told how much money the Norwegian Govt. is putting into Trial?

About "two and six"?

http://wiki.answers.com/Q/How_much_is_2_Shillings_and_Sixpence_worth_in_Euro_today

</halfjoke>

 

[heapsreal]

Levamisole can shift back to th1 and is much cheaper.

levamisole causes neutropenia so one will have to be very careful if they have bacterial co-infections. This is also an issue with rituximab too. This can also occurr with valcyte and is one reason why patients are monitored closely.

I still dont think theres going to be a one hit wonder.

Maybe i have missed some posts etc but beside the initial news that came out of norway, we just dont seem to be hearing from many on its success. Im really not sure its an autoimmune illness but more an immune defiency, so i think drugs like rituximab that knock out parts of the immune system just dont make sense and seems it could be quite dangerous in cfs/me since many of us have bacterial co-infections which i think could turn on us. Recent research shows that our nk cells dont work as well as our cd8 t cells and i think knocking out b-cells will just leave our defences too open. Im thinking that one is going to have to be sure to be tested for every infection(active) and treat them before turning to drugs like rituximab. If we just had parts of our immune system overactive then it makes some sense but generally we have parts of our immune system overactive and parts underactive, which to me paints a picture of a chronic infection/s with a burnt out immune system.

definately more research needs to be done with patients on rituximab and then being closely monitored. My opinion now is i wouldnt take it unless every infection i had was treated. Even with the small amount of info on rituximab and cfs/me there should be patterns appearing and should be available to those wanting to try ritux so they can then make a more informed decision. sub group, sub group, sub groups.

cheers!!!

 

[lansbergen]

But does it correct the autoantibodies, oxidative stress and abnormal cytokines? Maybe some cytokines, but I doubt much more.

The point is that rituximab, under what I proposed, eliminates the problem at least temporarily, and that other factors can be treated to improve this response, perhaps all the way to cure. This is of course only speculation at this point. What we do know is that it results in substantive remission of symptoms. I don't think levamisole does that.

Furthermore it should not be forgotten that at least a subgroup of ME does not (currently) respond to Rituximab, and either this is because Rituximab is not addressing the central issue, or ME is a mix of two different cohorts, or both.

My improverment on levamisole is very slow.

It decreases autoantibodies in several diseases, decreases HIV infectivity in vitro, has antitumor porportion, abolishes superoxide ions production and kills immunecells.

When the immunecell titer becomes too low stopping levamisole will restore it to normal.

 

[lansbergen]

levamisole causes neutropenia so one will have to be very careful if they have bacterial co-infections. This is also an issue with rituximab too. This can also occurr with valcyte and is one reason why patients are monitored closely.

Right but stopping levamisole will restore it. Rituxumab works much longer and in my opion for that reason is more risky

 

[heapsreal]

Right but stopping levamisole will restore it. Rituxumab works much longer and in my opion for that reason is more risky

Interesting, so if neutropenia occurrs it will recover quicker?

 

[lansbergen]

Interesting, so if neutropenia occurrs it will recover quicker?

When it is caused by levamisole is will reverse when levamisole is stopped.

 

[Gijs]

''Rituximab plus antioxidants plus antivirals could be a cure''

This will only take the secondary problems away but not the key problem. The proof for my statement is that your problems will come back. But it is important to treat the immune system for the long term. Because when your immune system is constantly attackt by ''things'' etc.. finally you will end up with ''mild'' problems like we see in untreated hiv/aids. I think that antioxidants and low doses anti viral medicine for herpes is safe and can be effective.

 

[snowathlete]

We are still left with the question of what caused the B-cell dysfunction in the first place, aren't we?
It must be something still present, which retriggers the disease again, or something fundamentaly altered that is not fixed by Rituximab, as we relapse when teh B-cells come back online.

 

[Firestormm]

We are still left with the question of what caused the B-cell dysfunction in the first place, aren't we?
It must be something still present, which retriggers the disease again, or something fundamentaly altered that is not fixed by Rituximab, as we relapse when teh B-cells come back online.

Could have been born with it I guess - you know? Or genetics. Doesn't need to be a virus specifically - not that that's what you mean - but a 'trigger' could set something off. Or something might not react the way it should to the trigger.

That's my simple-speak. It was all getting too technical for me around here

 

[lansbergen]

We are still left with the question of what caused the B-cell dysfunction in the first place, aren't we?
It must be something still present, which retriggers the disease again, or something fundamentaly altered that is not fixed by Rituximab, as we relapse when teh B-cells come back online.

Right. I thnk the primairy infection is still there and then I do not mean all the opportunists.

 

[MeSci]

I have said this on two other threads, but it belongs here too. I am looking at the question as to whether methylation or oxidative stress might drive the autoimmune issues. Both deplete glutathione. B cells that are glutathione deficient will not be able to make properly folded antibodies, as glutathione is needed to make sulfide bridges. I suspect that this will often inactivate the antibody, but it may also create antibodies with low or altered specificity, resulting in attacking self proteins. This would generate a very broad range of antibody targets, degrading capacity in many systems simultaneously, while also creating issues unique to individuals. It might also fit with the failure of rituximab to induce cure in many patients, as the underlying metabolic problem is not corrected. It is a testable hypothesis. Its also means that correcting oxidative and nitrosative stress might boost rituximab results. I wonder what would happen if this approach was used and included antivirals?

Cells usually have a capacity to destroy improperly folded proteins, and antibodies are proteins. However I do not know if this is right for B cells, or if they can be deranged in other ways that do this including infection. It may be that antibody production is different, or that the machinery that destroys bad proteins is failing.

What I expect to see if this hypothesis is right is large numbers of autoantibodies of different types, with different targets, but with poor binding properties.

Apologies if this has been posted here before - I may have even found it here - but this is a review paper on ME and autoimmunity:

http://www.investinme.org/Documents...s_and_parallels_with_autoimmune_disorders.pdf

 

[natasa778]

''Rituximab plus antioxidants plus antivirals could be a cure''

This will only take the secondary problems away but not the key problem. The proof for my statement is that your problems will come back.

Not necessarily. There is a number of patients, at least as reported in Phase I of Rituximab trial, that recovered completely and are healthy and active many years after their last infusion.

 

[Bob]

A new update re funding for the Norwegian Rituximab trial.
It seems that they've got all the funding they needed, and more:
http://mariasmetode.no/2013/11/update-haukeland-english/

 

[Esther12]

Well done to all involved.