Rituximab, the THRESHOLD theory

[redo]

Now that the news has broke, we're allowed to discuss the findings of Mella/Fluge. In the presentation in London they had out a poster of how they think (and they did emphasis think several times, as they don't know yet - this is only a theory of their's - such as in loose thoughts trying to work out why) the CFS symptoms are mediated.

Some respond early and for a long time. Long response.
Some respond short and late.
Some have no response from two infusions (about 1/3 don't have that)
Some respond, and do so for years and years after only two infusions.

Why?

Their theory is that when the Rituximab is given, it brings down the B-cells, but when that goes down, so does some other immune parameter of which they haven't identified yet. That doesn't mean that it isn't a known immune parameter, it means they don't know which it might be yet. That is displayed as "x" in the graph.

The way people get better is displayed with a green line, the higher it goes, the easier are the symptoms. The yellow line indicates the immunlogical thershold x needs to be under for the patient to feel better. It makes perfect sense to me. Although I as well, emphasize that it's a theory.

**********

The thoughts they presented at the conference, was that x might be an autoantibody. But they don't know yet. And they emphasized that it's something they're looking at. They had been checking loads of immune parameters before, during and after the infusions, but no clear picture emerged as to what could be behind this.

 

[snowathlete]

Very interesting.
Its great that they have somewhere solid to look.

Also, some patients relapsing is probably great when it comes to research, because they have a problem set of data at the begining and at the end, to compare against they recovery period. As apposed to only the one change that you get with someone who remains healthy.

Anyone got any guesses as to what it might be?


Something i havent picked up on yet, is why was there a barr on reporting this stuff?

 

[Sasha]

Something i havent picked up on yet, is why was there a barr on reporting this stuff?

Hi snowathlete - it was a publication embargo. Researchers generally request no online discussion of their findings before they've published them - otherwise, it damages their chances of publication. The study was published in PlosOne last week, so we can talk about it now.

 

[fla]

Glutathione?

 

[richvank]

Glutathione?

I think you are essentially right on, fla. Inflammation and oxidative stress go down (parameter x) and that allows glutathione to go up.

Rich

 

[Sean]

Hey, look here, some science is happening!

 

[barbc56]

Hi snowathlete - it was a publication embargo. Researchers generally request no online discussion of their findings before they've published them - otherwise, it damages their chances of publication. The study was published in PlosOne last week, so we can talk about it now.

I've always thought that this is a strange practice. It's okay to present something at a conference but not to talk about it elsewhere. What are the odds that something won't leak, although in this case it looks surprisingly like it didn't.

It seems backwards, but maybe there is a plausible explanation to all this that I am not getting. Wouldn't be the first time,

Anyone know why?


ETA Thanks redo!

 

[SilverbladeTE]

Hey, look here, some science is happening!

NO ONE EXPECTS THE NORWEGIAN INQUISITION!

All your ME are belong to us!

Go, go Good Team!

(meant in light hearted positive way)

 

[kurt]

All your ME are belong to us!
(meant in light hearted positive way)

LOL, you must be a gamer (or must have been...). I never heard this before my teenage son explained it to me. Yes, it does seem they are the 'boss' right now!

 

[kurt]

The thoughts they presented at the conference, was that x might be an autoantibody. But they don't know yet. And they emphasized that it's something they're looking at. They had been checking loads of immune parameters before, during and after the infusions, but no clear picture emerged as to what could be behind this.

I noticed in the video from Norway they mentioned that they believed the autoantibody target might be the sensory nerves. Do you recall if that was mentioned in the London presentation?

 

[Sean]

NO ONE EXPECTS THE NORWEGIAN INQUISITION!

 

[SilverbladeTE]

LOL, you must be a gamer (or must have been...). I never heard this before my teenage son explained it to me. Yes, it does seem they are the 'boss' right now!

Yup
never played that particular game, but that phrase "All your base are belong to us!" became a huge internet meme especially on gaming sites a few years back, lol

"Go, go Good team!" is from Everquest's early days
http://www.notacult.com/fansythefamous.htm
one man's famous fight against the forces of darkness! How did he defeat 350 bad guy players in one go? he got all the monsters to chase him, hundreds of them, dozens of giants too, and ran them right over the bad guys who got stomped into toe jam!
so in this sense, the "Good Team" are pulling (which is called "training" in games) the evidence, neutral observers, patients etc all over the Psychobabblers

 

[redo]

I noticed in the video from Norway they mentioned that they believed the autoantibody target might be the sensory nerves. Do you recall if that was mentioned in the London presentation?

I remember they said they thought the immune parameter which where "acting out" had the effect of sensory distortiong and sensory amplification, but not specifically that it might target the nerves. I haven't seen the video from Norway, only the one from London (and I only saw the Mella/Fluge part). Do you have a link to the video from Norway?

 

[SilverbladeTE]

Redo
As said before, I've had both meningitis and two-week long period of low blood sugar, and both had very similar sensations ot some of the ME exerience, in regards to how light/sound/multitasking "Hit" you so damn unpleasantly, like a gong ringing up your nerves or through head, barf!
So, while anectodatal it is good comparitive info as have many others, over the years to show ME has such effects

also, snake venoms can do the same from survivors tales (over stimulation to point of excruciating pain from any stimulus), hence they've been investigated for treatments for diseases that reduce nerve function.

 

[Spring]

What about Nagalase? For me it would make sense.

 

[Snow Leopard]

The open trials they are conducting at the moment are for the purpose of examining immune parameters right? Rather than to establish efficacy (which requires double blind RCTs to be convincing).

Where did you find that image by the way?

 

[redo]

No. The purpose is to see if patients benefit more from Rituximab (RTX) therapy with maintenance treatment. Those in the trials discussed in PLoS ONE where given only the two starter infusions, and they suspect that the 1/3 of patients not responding (such as in the recently published trial) will get better if they are given maintenance treatment instead of only two infusions. They are also doing blood transfusion on some of the worst patients before the RTX, and the purpose of that is to see if you "clean out" potentially abnormally high levels of some immune parameters before the RTX, will that make the worst patients improve enough that they'll get back their life.

They have already have sampled blood and whatnot from the patients from the first trials, so they have reference points from before/after/during the trials. So I assume they can test that for whatever they'd like... They are asking for others to do trials, because another researcher, another country (or continent) given RTX to ME patients would contribute to confirming/denying that it works. I assume that both open and blinded trials would help for the latter purpose, but of course, blinded trials would be best.

 

[*GG*]

I've always thought that this is a strange practice. It's okay to present something at a conference but not to talk about it elsewhere. What are the odds that something won't leak, although in this case it looks surprisingly like it didn't.

It seems backwards, but maybe there is a plausible explanation to all this that I am not getting. Wouldn't be the first time,

Anyone know why?


ETA Thanks redo!

Not sure myself, but perhaps to gather attention (some "buzz") and/or to entice someone to pay attention to publish?

GG

 

[redo]

I know you get a lot of praise for your moderation and all Dainty. But I think it's common decency to send a PM about why and when something has been removed. It's just by chance that I saw it, as I normally browse to the end right away. And I also think it's common courtesy to reply when I ask you to move a thread.

You could be all busy and everything. Hands full. Sick, tired, I get all of that. But at the same time, saying you're too tired to look into the issue would be fine.

About your

"moderation: image removed due to copyright infringement. Please be mindful, folks - thanks!"

Well, the London conferance doesn't have copyright to the image, as it's not from them I got it. If you think that something discussed in a conference shouldn't be up for discussion in public, that's fine. No problem. There could be many legitimate reasons for that. But that's a whole other issue.

 

[Sam Carter]

I know you get a lot of praise for your moderation and all Dainty. But I think it's common decency to send a PM about why and when something has been removed. It's just by chance that I saw it, as I normally browse to the end right away. And I also think it's common courtesy to reply when I ask you to move a thread.

You could be all busy and everything. Hands full. Sick, tired, I get all of that. But at the same time, saying you're too tired to look into the issue would be fine.

About your

Well, the London conferance doesn't have copyright to the image, as it's not from them I got it. If you think that something discussed in a conference shouldn't be up for discussion in public, that's fine. No problem. There could be many legitimate reasons for that. But that's a whole other issue.

I have to agree with redo whilst, of course, acknowledging the difficulties of moderation -- it must be something of a Sisyphean task.

However, the Mella and Fluge study is of such importance that if *copyright* prevents its proper debate then *copyright* should be ignored.

Please restore the deleted image.