Rituximab Phase III - Negative result

[Martin aka paused||M.E.]

@pamojja Okay I think got you wrong with the natural treatment options. Sorry

 

[Ben H]

Ah ok, I’m out of date. I just wish they’d go ahead and start formally publishing these findings rather than rely on YouTube updates or similar.

Hi @Londinium

The findings are far too preiminary to formally publish. They are working hard however to provide patients with updates (as in the last video/new series) even if they are preliminary so that everyone is kept informed. If they didn't do that, nothing may be heard for months on end. As a patient myself, personally I'd prefer to be regularly updated even if it wasn't formal (one reason we started the bedside chats etc).

The team are working hard on publishing their findings now in a journal. As @Bander said-very well-its about striking a balance.


B

 

[Cam Newton]

I wonder how bad the side effects of cyclo are. I would happily go through 6 months of nausea and mouth sores for a substantial improvement. On the other hand, if people got life threatening complications via a secondary infection, I’d prefer to wait a few more years for another alternative.

 

[Gingergrrl]

Re: Cell Trend, one of my closest friends from PR, who has not posted in approx 2 yrs, and was so ill he was in hospital for 4+ months, tested negative on all nine autoantibodies.

I know at least ten others who test positive for only 1-2 Cell Trend autoantibodies and a few others who test positive for 3-4 of them.

I only know of only one other person who tests positive for 7 of the 9 (like me) and I ran the test twice (once myself from a local speciality lab with my name and once my doc sending the blood from his office without my name) and both times I was positive for 7/9. I know one person positive for 8/9 and no one (yet) positive for all nine.

This test is measuring autoantibodies for beta adrenergic (autoimmune POTS) and other issues that affect dysautonomia and cholinergic/ muscarinic receptors. It may be totally irrelevant in the end to ME/CFS but it definitely helps show if someone is autoimmune and was relevant to my case and my treatment.

 

[halcyon]

And how would you explain that Ron Davis and his team found the same anomalies in metabolism in every ME patient and that his nano-chip also works in every ME patient?

This test has not been used on patients with other diseases to date. It may not be able to differentiate between people with MS and ME for example (or even depression.) I think you'll be hard pressed to find a chronic immune mediated disease that does not feature abnormal metabolism.

 

[bspg]

And how would you explain that Ron Davis and his team found the same anomalies in metabolism in every ME patient and that his nano-chip also works in every ME patient?

As far as I understand, the metabolomics were only done in the severely ill study and they weren't exactly the same between patients. I could be wrong though...

Also, the nano chip only measures electrical impedence and it's possible this could be altered in many different diseases. Its brand new technology so we don't know what diseases cause impedence vs. which do not.

 

[pibee]

Re: Cell Trend, one of my closest friends from PR, who has not posted in approx 2 yrs, and was so ill he was in hospital for 4+ months, tested negative on all nine autoantibodies.

I know at least ten others who test positive for only 1-2 Cell Trend autoantibodies and a few others who test positive for 3-4 of them.

I only know of only one other person who tests positive for 7 of the 9 (like me) and I ran the test twice (once myself from a local speciality lab with my name and once my doc sending the blood from his office without my name) and both times I was positive for 7/9. I know one person positive for 8/9 and no one (yet) positive for all nine.

This test is measuring autoantibodies for beta adrenergic (autoimmune POTS) and other issues that affect dysautonomia and cholinergic/ muscarinic receptors. It may be totally irrelevant in the end to ME/CFS but it definitely helps show if someone is autoimmune and was relevant to my case and my treatment.

As you know, I test highly pos for 8 and yet I dont even have POTS, I have mild ortostatic hypotension, which makes me prefer laying whenever I can but I don't feel problems when I sit or stand and walk, at least not heart related or no dizziness, lightheadedness (maybe very low because as soon as I'm home I half lay and all work or movies I watch are from half laying).

I do have a type dysautonomia, high-flow subtype maybe because my feet and palms tend to be hot, not cold.

I guess other factors are at play as maybe genes and lower numbers of receptors (wasnt this also something Australian team was researching?!)..

I think in my case severe cognitive, psychomotor and sleep disorder as well some psychiatric could even be linked to these antibodies as they've found some also in schizophrenia, especially in cogntive problems that precede psychosis and real sch.
So who knows what other broad antineuronal autoimmunity this test measures.
My brain si like bomb exploded there, hope its linked to CellTrend results. But after rituxME negative I'm now vey afraid of rituximab option (plus, I'd have to pay it) čbecause now we have again not much evidence ME is autoimmune. ..
And if you look Loebel et al, 1-3 of 100 healthy controls had very high results too, on Celltrend.

 

[Rossy191276]

Study dont get funded if product cant be patented.
If one double blind placebo showed IVIG at 2g/kg worked for 40% of CFS, why there wasnt a study later?
Only 3 studies, all together, all small.
Same with other natural treatments. Which doent mean they work.

I missed the post on this study... is it possible for someone to provide the link? Thanks

 

[Murph]

Hi @Londinium

The findings are far too preiminary to formally publish. They are working hard however to provide patients with updates (as in the last video/new series) even if they are preliminary so that everyone is kept informed. If they didn't do that, nothing may be heard for months on end. As a patient myself, personally I'd prefer to be regularly updated even if it wasn't formal (one reason we started the bedside chats etc).

The team are working hard on publishing their findings now in a journal. As @Bander said-very well-its about striking a balance.


B

I can sort of see why there is a reluctance by some scientists to mention their results informally. Lots of people seem to have become very invested in the results of this nanoneedle. Sample sizes are still tiny.

There is even something similar with this ritux update. 'Not significantly effective at primary endpoint on average' does not equal 'completely useless' if it hits a non-primary measure of success or works for a definable subgroup.

If people believe in a preliminary result too much then the scientists face backlash when later results come in different.

it is important to cultivate a way of approaching scientific findings that allows for them to be limited, provisional and uncertain.

 

[notmyself]

Looking to Rituximab to provide a cure for everyone with ME or CFS is like supposing other treatments that have helped some will work on everybody. ME and CFS is really just a group of symptoms that the Medics have stuck together to make life easier for themselves.

you couldn't be more right! it will never be something that will work for us all,because we have differrent problems wich cause simmilar symptoms..if we all have the same disease we will all respond in a simmilar way to certain suplemments and treatments, but we have so many examples when a suplement or treatment help someone a lot and make other much worse,both with ME..how is that even possible?!?!..there is no disease that work like this..it's clear that this is individual,is not the same disease..

 

[alex3619]

This test has not been used on patients with other diseases to date.

This is part of the issue. The test appears to have high sensitivity, or the capacity to detect ME. Or does it? More accurately it is detecting some kind of pathology. We have no idea if that pathology is unique to ME. So its right to say other disease groups need to be tested. That is about specificity, or the surety its not some other disease or pathology they are finding. While we have several very sensitive tests right now we have no formal assurance these problems are not found in many diseases.

This brings me to a point I have made many times now. While we cannot say this test can diagnose ME, it does show abnormal cell function. That is enough to demonstrate a very real biological disease, unless there is something going wrong that is not biological, like sample preparation problems, but this would presumably have shown up on controls.

We need to find out what is actually going wrong in the cells, then find out if there are other diseases this can be found in. If we understand the cell mechanisms, and do not find it in other diseases, then we would be well on the way to a cheap and accurate blood test.

 

[pibee]

I missed the post on this study... is it possible for someone to provide the link? Thanks

https://paolomaccallini.wordpress.c...mmunoglobulin-therapy-in-patients-with-mecfs/

 

[alex3619]

ME and CFS is really just a group of symptoms that the Medics have stuck together to make life easier for themselves.

CFS, definitely. ME might be like that, but it is not clear. The clearest example you can use to show this problem is depression. Depression, fatigue and pain are symptoms of disease, not diseases. Any diagnosis based mainly on one of these three, or any combination of these three, is problematic. Depression can be caused by many things, and its a category mistake to think its a discrete diagnostic entity. One can diagnose the symptom, but cannot diagnose the disorder or disease without making this error.

We also need to be careful about confusing a kludged disease category with any underlying disorder. ME may be many disorders, or one, but if its kludged with other diseases to create a bogus category it is not evidence that ME is not a discrete disease category, or several.

A similar mistake is made in medicine when they find nothing wrong with us using standard tests designed for other problems. Its also a problem when they have no test for ME and yet conclude there is nothing wrong with patients. They have to pay attention to the science, and most don't know the latest science, and test for what is testable. The first test that is proven to be useful dates from 1940, and that is the tilt table test. We can show specific problems even if we cannot diagnose ME using a test. So anyone making these claims that nothing can be found is about 77 years out of date. To be fair though, detecting OI in ME was not validated till 1995. But even if you use this date then doctors are still 22 years out of date.

 

[EtherSpin]

Fascinating. A pet theory of mine (which I will discard like that if evidence comes in!) is an endothelial problem.

I can create super PEM by combining two or more of these ingredients: alcohol, exercise, and sushine. (Combining all three is a mistake I made one fine day during a remission and boy was it costly.) It took me a while but I realised they are linked as causes of vasodilation. (They may be linked by other things too, of course).

This excellent presentation by a blood pressure expert was influential. POTS is huge for us and he explains why very clearly.

Fluge and Mella's NO patent also focused me in on the issue.

There might even be a link with purinergic singalling problems. Red blood cells release ATP when they hit areas of turbulence in the blood vessels and that helps expand those blood vessels in the right places. I don't see exactly the link from weak flow mediated dilation to Naviaux's purinergic signalling theory but there may be one. Systemic ATP shortage? idk.

Bearing in mind he will boldly tell patients that he can address all major CFS issues with moderating BP.
He said to my face that brain fog, muscle fatigue,light sensitivity,sound sensitivity and something else were all down to blood delivery in this illness ( he was being all dynamic and popping a finger up for each of 5 core problems he identified) and that I should be able to be fixed IF they have the right drug combination to keep my BP in sensible ranges. Turns out they didn't , I couldn't discern benefit from midodrine cause the skin crawl stressed me enough to subtract any energy gain i might have got from it.

- just thought I'd chip in cause yes, his presentations,ideas and manner are intriguing BUT he stretches it all so that his field can supposedly fix CFS and besides my own lack of success I know a couple of other people who were fully convinced he would help them then broke down in his office when he told them suddenly that they'd exhausted all options and he had nothing further.

 

[EtherSpin]

That is very interesting but I am not sure it correlates with what Dr Lipkin and Maddy Hornig found in their study a couple of years ago where the patients who had the illness for less than 3 years looked very different from those with longer duration?

Pam

I think Davis was talking metabolic VS immune activity from Hornig and co - wasn't the latter like 3 years of under activity followed by a switch to over activity? Could have been exact reverse of that. (My brain)

 

[Martin aka paused||M.E.]

This test has not been used on patients with other diseases to date. It may not be able to differentiate between people with MS and ME for example (or even depression.) I think you'll be hard pressed to find a chronic immune mediated disease that does not feature abnormal metabolism.

@Ben H That would be a great question for Ron and his team, maybe for your upcoming bedside story: Why does he think, that his findings in metabolism is special in ME? Has he used the chip on other diseases too? And are those anomalies in metabolism the same in all severely ill patients?

And to add a hot discussed topic: Why do you think, ME is only one disease? There are many people on PR thinking that we all have different diseases that only have the same symptoms. I think, we are divided into subgroups.

Thank you

 

[Gingergrrl]

As you know, I test highly pos for 8 and yet I dont even have POTS, I have mild ortostatic hypotension, which makes me prefer laying whenever I can but I don't feel problems when I sit or stand and walk, at least not heart related or no dizziness, lightheadedness (maybe very low because as soon as I'm home I half lay and all work or movies I watch are from half laying).

I couldn't remember if you had 7 or 8 positives. From the small sample size that I am gathering of people who have done Cell Trend testing, either from PR or other groups, my anecdotal results are that the people who are positive for Cell Trend Abs, are also positive for other autoantibodies, such as Mayo, Cunningham Panel, etc. Vs. the people who were completely negative on 9/9 Cell Trend Abs, were negative on all Abs, including common ones like the Hashi's Abs. So it seems like the Cell Trend tests are positive in those who already meet an autoimmune profile (vs. it meaning that every single person with positives has POTS). But like I said, this is just anecdotal so far.

I think in my case severe cognitive, psychomotor and sleep disorder as well some psychiatric could even be linked to these antibodies as they've found some also in schizophrenia, especially in cogntive problems that precede psychosis

Do you test positive for anti NMDA, or other brain autoantibodies, besides Cell Trend?

This brings me to a point I have made many times now. While we cannot say this test can diagnose ME, it does show abnormal cell function. That is enough to demonstrate a very real biological disease, unless there is something going wrong that is not biological, like sample preparation problems, but this would presumably have shown up on controls.

We need to find out what is actually going wrong in the cells, then find out if there are other diseases this can be found in.

These are excellent points, Alex, and you are so smart ... for real and I'm not being sarcastic. I am hoping that Dr. Davis has tested people with other diseases on the nano-chip (or nano-needle?) as a comparison.

 

[Martin aka paused||M.E.]

you couldn't be more right! it will never be something that will work for us all,because we have differrent problems wich cause simmilar symptoms..if we all have the same disease we will all respond in a simmilar way to certain suplemments and treatments, but we have so many examples when a suplement or treatment help someone a lot and make other much worse,both with ME..how is that even possible?!?!..there is no disease that work like this..it's clear that this is individual,is not the same disease..

That is one hypothesis. But I am not sure if your argumentation is compelling.

Just take psoriasis: There are many patients who do not respond to MTX and certain biologicals. There are even patients that have no response to topical cortisone. But there is no doubt they have psoriasis. And many of them report remissions for the first time with brand new biologicals (secukinumab, Ixekizumab...)
And with alternative treatments they respond very very differently. Most do not respond to supplements or specific diets at all while others have great improvements...

But they all have psoriasis!

 

[Londinium]

I can sort of see why there is a reluctance by some scientists to mention their results informally. Lots of people seem to have become very invested in the results of this nanoneedle. Sample sizes are still tiny.

There is even something similar with this ritux update. 'Not significantly effective at primary endpoint on average' does not equal 'completely useless' if it hits a non-primary measure of success or works for a definable subgroup.

If people believe in a preliminary result too much then the scientists face backlash when later results come in different.

it is important to cultivate a way of approaching scientific findings that allows for them to be limited, provisional and uncertain.

I think you’ve articulated what I was trying to say far better than I got across. I understand why the Stanford team want to share early results (and they are fascinating) but whilst they remain unpublished we shouldn’t read too much into them. Which is why I’m so impatient to see them in a peer-reviewed publication.

Edit: same applies to the Rituximab study. It’s too early to say whether this negative result means Rituximab is a dead end or whether further testing is warranted in the future, pending seeing the actual paper.

 

[gregh286]

Bearing in mind he will boldly tell patients that he can address all major CFS issues with moderating BP.
He said to my face that brain fog, muscle fatigue,light sensitivity,sound sensitivity and something else were all down to blood delivery in this illness ( he was being all dynamic and popping a finger up for each of 5 core problems he identified) and that I should be able to be fixed IF they have the right drug combination to keep my BP in sensible ranges. Turns out they didn't , I couldn't discern benefit from midodrine cause the skin crawl stressed me enough to subtract any energy gain i might have got from it.

- just thought I'd chip in cause yes, his presentations,ideas and manner are intriguing BUT he stretches it all so that his field can supposedly fix CFS and besides my own lack of success I know a couple of other people who were fully convinced he would help them then broke down in his office when he told them suddenly that they'd exhausted all options and he had nothing further.

Endothelium receptor dysregulation.
I wear fitbit in golf.
If i start moving and HR rises gently from 60 to 75/80 during round i know im in for easy day and low or no PEM.
If i start and i look at hole 2 its at 100+ then holy shit am i in for PEM.
Its like body loses ability to maintain BP homeostatis through NO synthesis.
When HR rises quickly under light exertion its bad sign for PWME. Body working way too hard for the physical effort required. Hence shit stamina.