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

[Boule de feu]

That's good that the story is starting to show up.

On the New Scientist report, they now state that they've removed the pejorative term "yuppie flu", which I'm pleased to see.

Wow, that IS crazy. LOL
Just kidding, Sasha. I could not resist.

P.S. I'm glad we had this discussion about the title. I did make a mistake in one of my titles once, and I was glad someone caught it before it got to the public. I'm sure UT will understand why we had such a discussion.

 

[Enid]

Crazy it aint - we have enough problems to concentrate in the UK without diversions into semantics or indeed personalities (assumimg all here seek the good for ALL who suffer).

 

[Sasha]

The story is in der Spiegel online, here.

Progress!

 

[Sasha]

I did make a mistake in one of my titles once

And I just put salt instead of sugar in my cocoa

 

[Enid]

Great news B de F - something making good headlines for you at long last.Your post 188.

 

[Dainty]

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.

There were two threads on the same subject that were merged together, both several pages long. Their titles were merged as well in order to reduce potential confusion as much as possible, since some members may rely on key words in a title to relocate threads.

Cultural confusion noted; the word "crazy" has now been changed to "astounding".

I continue to request that both initial and any further concerns be brought to moderators privately rather than pulling threads off topic with their discussion. Remember, we can't read everything.

 

[Clodomir]

You mean that someone like Simon Wessely will run a study on his patients and then declare that it doesn't work.....

are you saying you would be suspicious if SM published next Tuesday the results of his 15-month study?

 

[Enid]

Thanks to you all for happy resolution on the title - so as not to bring more awfulness against us all. Thanks urbantravels - not the wit or humour the anti's would understand I think.

 

[Insomniac]

Yep, Bio,

I want to point out that Dr Bell was also at the conference where the Norwegians gave their presentation, and he talked about the follow-up of the Lyndonville cohort.

Now - there you had an infectious outbreak spreading thrrough a population leaving ME/CFS in its wake.

Dr Bell followed up the children for years, until adulthood. They had typical ME.

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

QUOTE]

Multiple Sclerosis has occurred in cluster outbreaks that are the same or similar to infectious outbreaks. One was on the Danish Faroes Islands between 1943 and 1949 when British troops arrived there in that previously isolated place.
Also some researchers speculate that there M.S might have an infectious cause because it's epidemicology and the numbers of people getting ill over the years with it is more similar to that of infectious deseases rather than a non infectious illness *

So here you've got a autoimmune illness that is possibly infectious.

The CFIDS Foundation has also said in it's newsletters that it thinks M.E is an autoimmune illness.

*Citations: John Kurtzke 1986 paper and a couple of things I read in a book called "The Rise and Fall of of Modern Medicine"

I'm more optimistic about this than I was about the XMRV virus.

 

[Sasha]

Cultural confusion noted; the word "crazy" has now been changed to "astounding".

Thanks, Dainty!

I continue to request that both initial and any further concerns be brought to moderators privately rather than pulling threads off topic with their discussion. Remember, we can't read everything.

Sorry, my fault!

 

[Sushi]

Hi all,

I have a question regarding the mechanism of action of Rituximab versus some of the immune modulators used by some ME/CFS patients.

My understanding is that Rituximabs effectiveness is through the depletion of B cells. Do any of the modulators like LDN, GcMAF, Nexavir, Cycloferon, etc. work on B cells, and if so, do they enhance or deplete the B cells?

All the best,

Sandra

Hi Sandra,

It is my understanding that GcMAF will kill infected B cells (I am not a scientist, but a patient taking GcMAF.) I raised this in a post directed to Rich, but I'd welcome clarification from anyone who knows the science. Of, course there is the question, "Infected with what?"

Some of us taking GcMAF have been told (and experienced) that when our B cell population returned to normal we would feel better. (Rather than the apparent "worse" that some patients in this trial felt.)

Anyone with scientific knowledge in this area? I'd appreciate your input.

Thanks!
Sushi

 

[Dreambirdie]

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.

Hey Rich--

Me too. I'd really like your take on this, especially the part I bolded.

I remember many years ago, I tested as having only one third the normal amount of B lymphocytes.
What's your experience with other ME/CFS patients and their B lymphocyte profiles?

 

[snowathlete]

Just to give my two pennies worth...

I think two thirds of patients improving on this drug, is a fantastic result! I would think that any scientist running a trial of a drug would bite your hand off for that ratio.
Especially in a group such as ME/CFS where, being a syndrome with unknown cause, you are definately going to get a small portion of patients who actually have something else. I would be surprised if it was as much as a third, but i would guess that 10% of us do not have ME/CFS, but have something similar - most likely a multitude of things.

Also, as it goes, i am not in the slightest bit surprised that it is pointing to an autoimmune illness. In my circumstanes, when i look at what i know for sure about my illness, it is that my immune system has gone very wrong. But as many people have already said - who cares what causes it as long as we get an effective treatment.
Also, at least its a few years away, as apposed to 7 or 8 years away, which i woudl guess it would be if it were a brand new drug that hasnt been used in the human population before.

In summary: I am delighted with the results of this trial, and i just hope we can all apply pressure on our governments to get things moving forward quickly.

Best
Joel

 

[kurt]

Joel,
Actually, the age of the drug could be a small problem at first, since the patent on Rituximab expires next year, Roche has reportedly shown no interest in sponsoring studies of its use for ME/CFS (a rational decision in a for-profit venture, they would get little return if generics come out next year). And they have known about this possibility since at least 2009 when the first success was reported... I think it probably was strategic for them to ignore this though, not due to any disbelief or problem with ME/CFS.

So we might have to wait for, who knows what. Maybe this loss of patent protection will be a good thing, and perhaps some generics will appear and someone will want to conduct a study, that might make treatment more affordable. But I think we are back to the same old problem of lack of acceptance and advocacy, lack of fairness in medical research funding, etc. Still, we now know something we did not before, new directions will appear, hopefully some treatments that do not require continual destruction of our B cells, we do need to be able to make some new antibodies from time to time. What is wrong with the B cells? I think that is a question to ask.

Agree with your comment on pressure on the governments. This is not the first time there has been evidence of biologic problems in ME/CFS, but maybe now that there has been more publicity for our cause the last few years we can make this one into more of an issue, if they do not respond.

 

[biophile]

livingwithcfids wrote: One person in the placebo group has made full recovery from ME/CFS for 2.5 years? How is this even possible?

One person out of 15 is about 7%. I don't want to speculate about whether that person had ME/CFS or not. I'd rather give benefit of the doubt and say 7% is similar to the rough 5% full recovery rate observed in broadly defined CFS (http://occmed.oxfordjournals.org/content/55/1/20.full.pdf).

kurt wrote:

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!

Nice summary. I haven't really thought about which one or combination is more probable.

Sasha wrote: Clearly much better results than PACE and unlike PACE, the authors appear to be being very transparent about what analyses were specified in the protocol and where they did additional analyses in the light of their results. Very much looking forward to seeing more Rituximab stuff getting going. Hope Cort or someone can produce a list of what's now in the pipeline and what those studies are looking at in terms of biomarkers, polymorphisms, etc.

ixchelkali wrote: 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.

The definition of "major" (positive) response seems OK but perhaps it could be considered a "moderate" overall improvement? The authors comment how symptoms seem to improve across the board too, correlating with biological measures. However, actigraphy would have been helpful too. I hope future larger studies employ it, rather than purchasing the equipment and taking baseline measurements and then actively refusing to take outcome measurements like PACE did. Rituximab seems to be safe too but some of the reported side effects from other sources sound scary, and those of us who are sensitive to drugs are natually concerned.

Sasha wrote: That's good that the story is starting to show up. On the New Scientist report, they now state that they've removed the pejorative term "yuppie flu", which I'm pleased to see.

Boule de feu wrote: Wow, that IS crazy. LOL. Just kidding, Sasha. I could not resist.

Yeah it was crazy! The original version of the article didn't just say it USED to be known as "yuppie flu" but IS known as yuppie flu in exactly the same way that people say "CFS, also known as ME". Sort of like if they said, "Cerebral palsy, also known as hysterical paralysis", or "Autism, also known as cold mother syndrome" (and just as discredited).

ukxmrv wrote: You mean that someone like Simon Wessely will run a study on his patients and then declare that it doesn't work..... ;-)

Clodomir wrote: Are you saying you would be suspicious if SM published next Tuesday the results of his 15-month study?

LOL, cheeky! The CDC will be first in line to run a study using Reeves' "chronic unwellness" criteria.

 

[Valentijn]

And I just put salt instead of sugar in my cocoa

I suppose it might help with orthostatic intolerance

 

[Megan]

Great news to see this study! I really hope it attracts good scientists to look at CFS. After the XMRV letdown I was concerned that we would all be allocated to the back burner once again (or more like off the stove completely).

But I do share the concern that some here have mentioned about how "major response" is defined. The paper says:

During follow-up, the patients recorded overall change in each symptom the preceding two weeks, as compared to baseline

A major response was defined as a Fatigue score >=4.5 for at least six consecutive weeks, also demanding recordings of some fatigue symptoms as major improvement (value 6) during the response period.

4 is "slight improvement" and 5 is "moderate improvement". That sounds like a major response is really somewhere between slight and moderate improvement. It seems patients have only had to additionally rate "some" fatigue symptoms (not their overall fatigue score) as "major improvement" on only one occasion within the 12 month period.


I am concerned about this because I know in my own case it is very easy to over rate where I'm at. If I was really getting better every time I thought I was then I'd be better by now. It's a bit like losing weight - when the weight is coming off it's easy to jump on the scales all the time and be super conscious of it, but when it creeps back on just put your head in the sand and pretent it's not happening.

 

[Esther12]

Just thinking aloud, trying to think of possible problems with the study (as inspired by Megan's post above): Depending upon how Rituximab works, is it possible it could be inducing some sort of affect as an active placebo, rather than as a treatment of autoimmune problems?

eg: The saline placebo would have had no affect. Maybe the Rituximab gave a bit of a 'buzz', and that led to patients tending to be more positive in reports of their symptoms?

A double blind trial is a good way of dealing with the problems of the placebo affect, and subjective measures of disability - but there are still potential problems with it. It's really difficult to measure disability and improvements with CFS, and that can end up sending us down dead ends.

 

[beaker]

Joel,
Actually, the age of the drug could be a small problem at first, since the patent on Rituximab expires next year, Roche has reportedly shown no interest in sponsoring studies of its use for ME/CFS (a rational decision in a for-profit venture, they would get little return if generics come out next year). And they have known about this possibility since at least 2009 when the first success was reported... I think it probably was strategic for them to ignore this though, not due to any disbelief or problem with ME/CFS.

So we might have to wait for, who knows what. Maybe this loss of patent protection will be a good thing, and perhaps some generics will appear and someone will want to conduct a study, that might make treatment more affordable. But I think we are back to the same old problem of lack of acceptance and advocacy, lack of fairness in medical research funding, etc. Still, we now know something we did not before, new directions will appear, hopefully some treatments that do not require continual destruction of our B cells, we do need to be able to make some new antibodies from time to time. What is wrong with the B cells? I think that is a question to ask.

Agree with your comment on pressure on the governments. This is not the first time there has been evidence of biologic problems in ME/CFS, but maybe now that there has been more publicity for our cause the last few years we can make this one into more of an issue, if they do not respond.

I was told by a researcher that with this med generics don't pose a problem b/c of it's nature as the type of biologic it is. It is what it is. My brain was not working well enough to retain an understanding of the science behind that. Perhaps someone else on here is able to do so ? That said, there are other drugs in the pipeline that are attempting to work in a similar fashion, but I am told that so far none of them come close to Rituxan in effectiveness.

 

[Sasha]

One person out of 15 is about 7%. I don't want to speculate about whether that person had ME/CFS or not. I'd rather give benefit of the doubt and say 7% is similar to the rough 5% full recovery rate observed in broadly defined CFS (http://occmed.oxfordjournals.org/content/55/1/20.full.pdf).

In regards to the one person in the placebo group who had the large and sustained improvement, the authors say in the full paper that one of the two placebo responders (i.e. a big response, including the one who looks as though they have recovered) didn't fit the Canadian criteria, only the Fukuda 1994 criteria. Also, of the three people who recovered (2 in the Rituximab group, 1 in the placebo group), two had been ill for pretty short periods: 8 months, and 12 months (the third for 5 years).

I wonder if the placebo "recovered" person was non-CCC and/or ill for a year or less; that would bring both spontaneous recovery and recovery from something other than ME into the frame.