Gingergrrl
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Rituximab Phase III - Negative result
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Hi [from memory] if you check out Alain Moreau's presentation at the OMF Symposium he refers to a group of people with ME/CFS who have an MiRNA which regulates the CD20 receptor which is up-regulated/down-regulated [or some such]. Rituximab targets CD20 B-cells; Alain and Fluge are going to work together on investigating whether this would identify a sub-group who are likely to respond to Rituximab. Alain's talk starts at 2:26:35 [https://livestream.com/accounts/1973198/ME-CFS-2018/videos/180981460].
pibee
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Any news on this?
Klimas group believes there is a sub group that will respond to rituximab. I believe there is a trial with better selected patients underway, but I could be wrong...
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I personally think the Norwegian researchers commit fraud. The difference between the first 2 trials and the last was so different, I suspect they fiddled the data of the first trials for extra funding for the last. This is common in scientific research. There’s a good article about how and why researchers do this. Sadly it’s very common too!
The good news is though that even if the study was fraudulent, the attention it brought to ME was huge. As the timing of new tools to measure our bodies by other unrelated researchers boomed because Rituximab was thought to prove ME was biologically. Luckily for us the unrelated researchers did indeed find massive amounts of biological differences in ME patients compared to controls. So even if the Norwegian researchers commit fraud,we still owe them gratitude for opening the floodgates into research. Timing was important too because technology finally caught up also. The evil psychiatrist Simon Weasley who suggested ME patients “didn’t want to get well” had to eat humble pie during the Rituximab trials, and then again he was shamed when other researchers showed so much unusual activity going on in the bodies of ME patients. So it’s a mixed blessing.
Disclaimer: I can’t be sure the first Rituximab trials were fraudulent I just highly suspect it.
I replied previously to you on this [https://forums.phoenixrising.me/ind...iii-negative-result.56244/page-17#post-987701].
Rituximab treatment is I assume based on the assumption that you're B-cell are producing autoantibodies i.e. which cause ME/CFS. The autoantibody test are c--p. However, one of the leading scientists (Carmen Scheibenbogen) who worked on these autoantibody tests recently published a paper showing that threes genes are upregulated in ME/CFS*. These 3 genes were able to separate a (small) group of people with ME/CFS from a (small) group of people who did not have ME/CFS i.e. healthy controls. I.e. a possible diagnostic test.
[*"The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome" - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x].
That's how science works i.e. try something fail, --fail -fail-- success. Ron Davis explained this in one of his talks; I guess this is why OMF are persuing so many different approaches.
Consider lobbying for funding; there are good scientists out there (including Fluge and Mella) but they need funding.
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JES
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Have you actually looked at the results they reported, for example this table that provides individual level patients data highlighting the improvement of many patients? My understanding from following PACE and other messy trials is that very rarely is there actually any direct data manipulation going on. What happened in PACE was that certain thresholds and ways of calculating outcomes were adjusted to make the results seem more impressive, but actual raw data wasn't manipulated.
Regarding manipulation of individual patient data like the one in the table I provided, I don't see how it would be feasible in this day and age. First of all, any patient in such a small trial group could probably recognize himself/herself in this data, so a widely different result would most likely immediately be spotted. It just doesn't make any sense even when assuming that the researchers were corrupt, which I don't see any evidence for either.
If you want to look for a reason behind the disparity in phase 2 and 3 results, IMO a lot more likely explanation is that the patient group was much bigger in 3. If we assume that ME/CFS may be caused by several mechanisms, maybe the small group of patients in phase 2 contained a larger portion of an autoimmune subgroup that responded to rituximab.
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Learner1
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Do you have a link that works, please?
ljimbo423
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Learner1
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Thanks! So, as @FMMM1 said, this is about a biomarker for detecting ME/CFS, I've and above the ones already found.
I'd be a lot more interested in a treatment here. If Rituximab isn't it, what is?
I'd be a lot more interested in a treatment here. If Rituximab isn't it, what is?
Hi I entered all of the following into a Google search and the first return is the paper:
The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome" - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x
Check out Vicky Whittemore's (NIH) presentation at the 2018 Invest in ME Conference.
From memory Vicky pointed out that in another illness she's involved with they've just found the causal gene. They can now develop drugs regarding that gene. ME/CFS isn't at that point i.e. the cause hasn't been identified with certainty.
On the flip side we may not need a drug. As Ron Davis has said the system may be intact; what we need is to find out how to re-set it.
Learner1
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I am not convinced we all have the same exact problem to solve. And there seem to be multiple genes involved, so changing the expression of or editing one gene is not the answer.
It does seem to be about understanding a system of interrelated systems that have gone awry and altering the levers to cause all of the little systems to behave better together so the whole concert is more harmonious.
And figuring out one or a few biomarkers is a very long way from being able to do this. The biomarkers are more like the contrail of a jet airplane - we know the jet made it and it points backward to where the jet came from, but we still can't figure out where its going, or if it has enough fuel to get there.
From what I understand, Rituximab is helping some patients, IVIG is helping some, Valcyte is helping some, nutritional supplements are helping some, avoiding and detoxifying mold and other toxins us helping some, surgery on spinal probkems is helping some. Which biomarker is going to tell us which intervention or interventions will help which patients?
Unfortunately, we are likely many years from these answers. I don't like it, and I know scientists are working as hard as they can. But, time is ticking away for all of us, and perhaps if one is 20 now, 5 or 10 or 15 or 20 years waiting for a cure gives one hope for fulfilling life afterwards at a younger age, but for those who are 1-4 decades older, adding this wait time for a cure doesn't give us much at the end...
While I agree that research should be done properly, papers should be published, collaboration should happen, as a patient, the only thing I find relevant is any info on what tests can be done today to give clues and speculation on what theories might work to fix us, so my doctors and I can evaluate the possible risks and rewards and pick and choose those interventions that seem to provide the best chance of success. I just don't see waiting month after month, year after year for all of this research to come to fruition. So far, taking all of the clues and making educated guesses has helped a lot, hasn't cured me, but has vastly improved my quality of life and ability to function. And, my doctors have found a surprisingly long list of various problems to solve that would not likely be resolved by a magic bullet. A process maybe, as Dr. Naviaux has discussed, but no miracle cure...
It does seem to be about understanding a system of interrelated systems that have gone awry and altering the levers to cause all of the little systems to behave better together so the whole concert is more harmonious.
And figuring out one or a few biomarkers is a very long way from being able to do this. The biomarkers are more like the contrail of a jet airplane - we know the jet made it and it points backward to where the jet came from, but we still can't figure out where its going, or if it has enough fuel to get there.
From what I understand, Rituximab is helping some patients, IVIG is helping some, Valcyte is helping some, nutritional supplements are helping some, avoiding and detoxifying mold and other toxins us helping some, surgery on spinal probkems is helping some. Which biomarker is going to tell us which intervention or interventions will help which patients?
Unfortunately, we are likely many years from these answers. I don't like it, and I know scientists are working as hard as they can. But, time is ticking away for all of us, and perhaps if one is 20 now, 5 or 10 or 15 or 20 years waiting for a cure gives one hope for fulfilling life afterwards at a younger age, but for those who are 1-4 decades older, adding this wait time for a cure doesn't give us much at the end...
While I agree that research should be done properly, papers should be published, collaboration should happen, as a patient, the only thing I find relevant is any info on what tests can be done today to give clues and speculation on what theories might work to fix us, so my doctors and I can evaluate the possible risks and rewards and pick and choose those interventions that seem to provide the best chance of success. I just don't see waiting month after month, year after year for all of this research to come to fruition. So far, taking all of the clues and making educated guesses has helped a lot, hasn't cured me, but has vastly improved my quality of life and ability to function. And, my doctors have found a surprisingly long list of various problems to solve that would not likely be resolved by a magic bullet. A process maybe, as Dr. Naviaux has discussed, but no miracle cure...
If you had those problems before developing ME, then curing ME probably wouldn't help. However, if the problems developed afterwards, then they might be resolved by curing or at least treating ME.
There's a lot I agree with in your post. However, (probably repeating myself) we don't know what's causing ME/CFS. Therefore, it could require the discovery of cause and the development of new drugs. The development of a drug from scratch might take 15 years. However, as Ron Davis has pointed out, we may not need a dug i.e. since the system appears to be intact - based on the nanoneedle results which reverse when you switch from ME/CFS plasma to control plasma. As you point out, it may be a reset issue. However, you can't say, with a high degree of confidence, that it will take 20 years or 2 years i.e. for an individual who is using this forum.
Ron Davis, and Jen Brea, debated time scale recently (last 1 year?) and the argument (from memory) was pretty much the one in my previous paragraph.
Gingergrrl
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I was wondering this as well and am hoping someone will tag me when the Phase 3 paper comes out (in case I miss it)!
I believe that as well and hope that there will be more research on this issue.
I disagree and why would they possibly commit fraud? Do you have any evidence to back up a statement like this? I would love to understand why the Phase 2 and Phase 3 results were so different but I do not believe that there was any sort of fraud.
I don't believe that all of the autoantibody tests are crap but I also believe that Rituximab may work in some patients in a mechanism that we just do not yet understand (in addition to B-cell depletion of autoantibodies).
I agree (either a larger portion of patients in an autoimmune sub-group or some patients with a misdiagnosed autoimmune disease). Which to me means it was a more obscure autoimmune disease vs. the more common ones which would be detected by mainstream testing.
I totally agree.
I've only skimmed through your response, but your comment that "a lot more likely explanation is that the patient group was much bigger in 3" seems sound. I'm guessing that if you looked at all phase 2, and phase 3, trials the data for this trial may well be within a few standard deviations of the mean.
I agree that rituximab may work in some people with ME/CFS. I was being simplistic when I said that all of the antibody tests were c--p but I think that there's some evidence of false positives/negatives. I think some of these tests should be reviewed and possibly an improved immunoassay produced or an alternative test (like mass spectrometry) produced. Ron Davis has done some work on improving immunoassays [https://www.omf.ngo/2018/02/12/tweak-assay-bolster-disease-detection-stanford-medicine-news-center/].
I agree i.e.there may be a number of causes of ME/CFS; check out Ron Tompkins's presentation at the OMF (2018) OMF Community Symposium. Ron says pretty much the same thing (from memory) i.e. diseases with different causes can end up at a common end point (outcome).
Gingergrrl
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I understood what you meant and I agree that these tests will be improved upon in the future. It is also frustrating that the only lab that runs these tests (as far as I know?) is in Germany. I don't understand why the US is so behind and there is no lab that offers these tests here. I am very grateful to Fluge & Mella, Dr. Scheibenbogen, and Cell Trend but I wish the US was more up to speed on all of this information! I was able to seek out what I needed (regardless what country or lab) but I know that many people are too ill to do this. I wish this information was not so fragmented!
charityfundraiser
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I am wondering if the idea has been considered that Rituximab might have worked in the first patients who had both CFS and cancer because it treated the cancer, and that the cancer might have been contributing to their CFS even before they were diagnosed with cancer.
I was treated this year for a different cancer (colon) with surgery and a different chemotherapy (FOLFOX), and about 6-9 months later, my fatigue is less and there is a difference in the characteristics of the fatigue in that my PEM is mild if any now.
I was treated this year for a different cancer (colon) with surgery and a different chemotherapy (FOLFOX), and about 6-9 months later, my fatigue is less and there is a difference in the characteristics of the fatigue in that my PEM is mild if any now.