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Article: Treatment Breakthrough (and Paradigm Shift) For CFS? Rituximab Trial Promises Hope

Thanks Cort - this was stunning news. I can't forget the work of Norwegian ME who raised the whole profile of ME over very many years as background to acceptance of the disease (I hear funds are in place now for the next stage of research). It has simply changed the landscape here - a disease not all in the mind proven.
 
While their cohort was originally assembled using the Fukuda definition, they later went back and applied the CCC. All but two patients also met that. Those two happened to be the two placebo responders. I think that is very significant.

Yes! Very interesting...I didn't get that in there - but that was very promising. Thanks for the reminder :)
 
Thanks Cort - this was stunning news. I can't forget the work of Norwegian ME who raised the whole profile of ME over very many years as background to acceptance of the disease (I hear funds are in place now for the next stage of research). It has simply changed the landscape here - a disease not all in the mind proven.

Yes, Enid, its amazing and gratifying to see this come out of Norway and to see the change that is occurring. You just never know where a breakthrough is going to come from.
 
Cort, again, fascinating article! I hope this study will get into discussion at the CFSAC meeting in November. It's interesting to note that while the 2011 NIH budget for ME/CFS is only $6 Million, the Autoimmune Diesease budget is $866 Million. It should be argued that funding for Rituximab trials (for starters) could hit that bucket.

see NIH budget by illness:
http://report.nih.gov/rcdc/categories/
 
SpecialK82, I agree with you about getting this subject into the CFSAC meeting in November. If it isn't on the agenda, I hope that someone testifying brings it up. Not sure how all this works, but we can't miss the chance to have this new line of research considered here!
 
Hi, Cort. I, too, appreciate your highlighting this study. I think it gives us an important clue. As you know, I have proposed the GD-MCB pathophysiology model for ME/CFS. While I may seem like a stuck record, I do think that the results of this study can be interpreted in the light of this model, as follows: 1. We know from past research on the immunology of ME/CFS that this disorder involves a Th2 immune shift. 2. This means that the B cells are overactive in ME/CFS, producing antibodies. 3. However, the B cells also promote inflammation, and because of the HPA axis dysfunction that is also present, the inflammation is not well controlled by cortisol. 4. When Rituximab knocked out B cells in the patients in this study, I suggest that it also lowered the inflammation. 5. Inflammation involves the production of oxidative stress by the oxidizing free radicals that are produced by cells of the immune system. 6. Lowering the inflammation therefore would also have lowered the oxidative stress. 7. Lowering the oxidative stress would have lowered the demand for glutathione, which is the basis for the antioxidant enzyme system. 8. Glutathione would therefore have risen. 9. I suggest that in some of the patients, at least, it rose enough to correct the vicious circle mechanism involving the functional deficiency of B12, the partial block in the methylation cycle, and draining of folate from the cells. 10. I suggest that this allowed the sulfur metabolism to return to normal, and when the B cells came back up some months later, it was able to remain normal, so that the patients experienced long-term recovery. 11. For the patients that relapsed, I suggest that the new B cells produced more inflammation than the glutathione could handle, so that the vicious circle was re-established. 12. For the patients that didn't receive any benefit, even short-term, I suggest that there were other factors that were holding down the glutathione, such as high body burdens of toxins. If this is true, it might mean that doing methylation treatment together with Rituximab might improve the odds for some of the patients, so that they could also experience long-term recovery. It would be very helpful if people doing Rituximab studies in ME/CFS would monitor glutathione. I think this would give the necessary data to explain the different outcomes of the patients. Best regards, Rich
 
Can I just mention Cort that the JC virus (PML) is not untreatable apparently - this is from Wikipedia (abstract)............ Needless to say I know nothing about Virology.http://jnnp.bmj.com/content/early/2010/06/19/jnnp.2009.190652.abstract

Also your article X drug CMX001 used by Dr Peterson in treatments - is shown successful too.http://www.businesswire.com/news/home/20101130005169/en/Cytheris-Announces-Publication-Clinical-Case-Study-Combining

I think I'm trying to suggest that if by any chance Rituxmab does reactivate the JC virus (dormant in large numbers I believe) it is treatable. Why blame a drug for this possibility.
 
Cort, again, fascinating article! I hope this study will get into discussion at the CFSAC meeting in November. It's interesting to note that while the 2011 NIH budget for ME/CFS is only $6 Million, the Autoimmune Diesease budget is $866 Million. It should be argued that funding for Rituximab trials (for starters) could hit that bucket.

see NIH budget by illness:
http://report.nih.gov/rcdc/categories/

I was wondering about that SpecialK :). Obviously there's the potential for us to hook into a group of disorders with a very large budget and lots of research. :cool:
 
Rich
if the b cells are over active producing antibodies, why do so many of us lack positive antibody titers to viruses .....which we likely have since we respond to antiviral treatments?
Thanks

Hi, aquarius.

Not sure. One thing that impedes the B cells is the folate draining. It takes folate to make new DNA, and that is necessary for proliferation of the B cells. Another factor is the elevated RNase-L. It could be chopping up the viral RNA fast enough to prevent the viruses from multiplying and traveling in the blood stream. If they don't get out there, the B cells will not find them and be able to respond to them.

Rich
 
Hi, Cort. I, too, appreciate your highlighting this study. I think it gives us an important clue. As you know, I have proposed the GD-MCB pathophysiology model for ME/CFS. While I may seem like a stuck record, I do think that the results of this study can be interpreted in the light of this model, as follows:

1. We know from past research on the immunology of ME/CFS that this disorder involves a Th2 immune shift.
2. This means that the B cells are overactive in ME/CFS, producing antibodies.
3. However, the B cells also promote inflammation, and because of the HPA axis dysfunction that is also present, the inflammation is not well controlled by cortisol.
4. When Rituximab knocked out B cells in the patients in this study, I suggest that it also lowered the inflammation. 5. Inflammation involves the production of oxidative stress by the oxidizing free radicals that are produced by cells of the immune system.
6. Lowering the inflammation therefore would also have lowered the oxidative stress.
7. Lowering the oxidative stress would have lowered the demand for glutathione, which is the basis for the antioxidant enzyme system.
8. Glutathione would therefore have risen.
9. I suggest that in some of the patients, at least, it rose enough to correct the vicious circle mechanism involving the functional deficiency of B12, the partial block in the methylation cycle, and draining of folate from the cells.
10. I suggest that this allowed the sulfur metabolism to return to normal, and when the B cells came back up some months later, it was able to remain normal, so that the patients experienced long-term recovery.
11. For the patients that relapsed, I suggest that the new B cells produced more inflammation than the glutathione could handle, so that the vicious circle was re-established.
12. For the patients that didn't receive any benefit, even short-term, I suggest that there were other factors that were holding down the glutathione, such as high body burdens of toxins. If this is true, it might mean that doing methylation treatment together with Rituximab might improve the odds for some of the patients, so that they could also experience long-term recovery. It would be very helpful if people doing Rituximab studies in ME/CFS would monitor glutathione. I think this would give the necessary data to explain the different outcomes of the patients. Best regards, Rich


3. However, the B cells also promote inflammation, and because of the HPA axis dysfunction that is also present, the inflammation is not well controlled by cortisol.
4. When Rituximab knocked out B cells in the patients in this study, I suggest that it also lowered the inflammation.

Interesting stuff Rich. I believe Maes is following a similar pathway - as in an email he stated he believed some CFS patients may have a reversible autoimmune disorder that is being driving by oxidative stress. His recent study suggested that people with CFS have an auto-immune response to the by-products of oxidation.
 
Cort said:
(A) similar (PCDBT) trial sent Dr. Montoya back to the drawing board for a couple of years to figure out what happened to fantastically successful first herpesvirus antiviral trial results.
I'm really looking forward to Montoya finally publishing his PCDBT on Valcyte, which he outlined in his widely circulated talk in March, 2011 so that you can get over comments like the one above. The first three patients in the early Rituximab trial were wildly successful compared to the latest Rituximab study. The two "CFS" patients that responded to the placebo in the Rituximab study apparently did not meet the Canadian Consensus Dx (CCD) criteria in a dost hoc analyses. Rituximab may be a huge clue as to an underlying mechanism in a SUBSET but 33% of patients had no response and all but two eventually relapsed. There are going to be a lot of questions about subsets and I believe that organizations hanging on to anything less than the CCD criteria are going to be revealed as having impeded progress out of a misguided fear of leaving anyone out.

Everyone is noise when their data is included in somebody else's cohort!

Montoya on Rituximab:
- I made an observation that Valcyte (anti-viral drugs) seemed to be working in some patients, and we have now completed a double-blind, controlled study showing that it works in a subset of patients. (In some patients, i)t does not work at all, and we must try to understand why. My hope is to find a biomarker that enables me to say "this patient needs anti-viral agents, while this patient need other medications," said Montoya, who says that the study he's talking about will soon be published. He believes that there may be immune response against various infections that cause symptoms, not the virus itself. - The idea behind what we have done with Valcyte is that we take away the immune system's excuse to attack. The infection pushes the immune system into an over-reaction. I think the solution to this will be a combination of controlling infections, but also to control the immune response, says Montoya. He believes the future lies in the combination therapy, and he hopes it may be possible to find very specific markers for the disease. - There are autoantibodies that are found in ME / CFS, but we have not found a specific autoantibody or a specific group of autoantibodies that can only be found in ME / CFS, says Montoya.
 
Cort, again, fascinating article! I hope this study will get into discussion at the CFSAC meeting in November. It's interesting to note that while the 2011 NIH budget for ME/CFS is only $6 Million, the Autoimmune Diesease budget is $866 Million. It should be argued that funding for Rituximab trials (for starters) could hit that bucket.

see NIH budget by illness:
http://report.nih.gov/rcdc/categories/

Excellent point. There are 23.5M Autiommune Disease patients in the US, per AARDA. So that NIH budget translates to about $37 per patient. Therefore a comparable and fair investment in ME/CFS research as an autoimmune disease would be at least a $37M annual NIH budget. Probably AARDA is already aware of this new research as well, maybe they can help make the case for more funding for ME/CFS...

FYI - I just emailed AARDA to suggest they add CFS to their autoimmune list, currently they say CFS has similar symptoms to an autoimmune disease but is not autoimmune. Maybe they need to re-think just why it is that CFS has similar symptoms to an autoimmune condition... Please, if forum members agree, also email AARDA, I think they are a potential strong ally for us.