Discussion in 'Phoenix Rising Articles' started by Mark, Sep 9, 2013.
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Congratulations Andy on your first article I shall return later once I caught some
Excellent article, Andrew!
As you say, Rituximab - whether as individuals we benefit from it or not - is having a hugely positive effect on research and has enormous potential for good for people with ME/CFS. But if we want the research to continue we have to donate.
Amazingly, the UK trial of 30 patients has already raised a third of the £350k funding needed, with £56k raised by IiME and a pledge of £60k from the MEA, subject to their normal peer-review process. The faster we throw money at this, the faster it will get done.
As I said in my article:
Donate! There are now two Rituximab funds raising money for this trial: Invest in ME's fund and the ME Association's fund (scroll down for donation instructions), and we can probably expect each collaborating ME charity to set up its own fund for the trial as they join in. UK taxpayers should Gift Aid their donations.
Join The Matrix (long black coat optional): be one of 100 people to make a pledge to raise £1,000.
Fundraise: people are doing all sorts of things to fundraise, from selling crafts to sponsored walks. Think about what you can do.
Raise awareness of the trial. Many people in the UK who have ME don’t belong to any of the charities and won’t know that there’s a trial to donate to or raise money for. Help them find out.
I didn't know Julia Newton was looking at Rituximab, Legendrew - do you have any more details?
Yeah - I don't believe she is looking directly at it for treatment of ME at the moment but she is looking into it for PBC and trying to understand how it effects fatigue mechanisms. always good when researchers have these things in mind!
"At the launch, Professor Newton will outline three new studies being carried out in Newcastle. The first involves examining whether a monoclonal antibody, Rituximab, could be used as a medicine in order to understand more about fatigue mechanisms. Rituximab is highly successful in treating rheumatoid arthritis, some cancers and the profound fatigue experienced by patients with an immune liver disease known as Primary Biliary Cirrhosis." comment taken from here: http://www.ncl.ac.uk/press.office/p...ether-to-discover-biological-causes-of-cfs-me
Also thank you for the positive feedback! I had quite a lot of fun writing this one and learnt a lot from it - hopefully the next one will be even better!
That's interesting that that comment suggests that Rituximab treats the profound fatigue but not the disease (unless I'm reading too much into that).
Yes, it's fun to write!
Congratulations on a fine debut, Andrew and I'm glad you enjoyed doing it (I sometimes find writing a painful process ).
Let's hope that Fluge & Mella's new Rituximab paper (looking at use of maintenance doses to prolong/make permanent the gains) is published soon. From what they said at the Invest at ME conference, it shouldn't be long now.
I wondered if you'd like the opportunity to expand a little on your thoughts here, Andy? I always used to say, that we were all in this big pot, but that as research honed in on the issues, we'd be siphoned off into smaller and more relevant pots. This seems to be what you are saying here.
However, looking at Rituximab and a disease like Rheumatoid Arthritis - that my mother has - the large pot might be said to be 'Arthritis' and the smaller pot - within the group - RA. But not all people with RA are treated with Rituximab. Indeed, my mother has only ever received symptom management medications, just as an example.
My point I suppose here is, that ME could be linked to some autoimmune mechanism, a test might reveal this in some people, and Rituximab might be determined for some people and not others: but under what circumstances do you think those people would be assigned to a new condition?
Hope that makes sense old bean. I am still knackered
Yeah that's the point i'm making - I think as time goes on the smaller groups will be siphoned off as you put it into groups with the same causation, given names more appropriate to the causal mechanism. By identifying an autoimmune group and isolating them you simplify this autoimmune condition while also simplifying ME by removing a group of patient for whom you now know the problem. It's a little confusing but both groups will end up getting treated better if we know the different causes.
To put it simply, if the broad subheading of ME today includes groups for whom different things are the cause: autoimmune, chronic viral, bacterial, psychological etc etc. By removing the autoimmune group you can give them better treatment and decide who to give rituximab (I doubt rituximab would help anyone for whom autoimmunity isn't the problem). The group then left under the heading of 'ME' are a more concentrated group with fewer different diseases meaning further research into ME will likely find more consistent findings and help with further siphoning.
It seems so simple to think but it's difficult to explain!
Good summary of the Rituximab context Andrew.
Thanks for the mention : ) which was followed by this :
"It is interesting to note that this could come as a result of the autoimmune process targeting the neurones of the sensory nervous system – as was originally proposed by Fluge and Mella following their 30 patient trial."
I hadn't realised that Fluge and Mella had suggested autoimmunity targeting the nervous system (or perhaps I'd just forgotten). Do you happen to know if they discussed this in any more detail or was it just a passing remark?
I believe that it was a fleeting comment in a Norway news piece on rituximab made by one of the doctors - i'll see if I can find it.
Edit: Video here - there are english subtitles you can turn on and i believe the comment is made at around 4 minutes in. I don't know how far they got with this theory but it's certainly an interesting idea.
Oh yeah it is
You see Rheumatiod Arthritis is not always diagnosed specifically by a test resulting in positive autoimmune disease:
e.g. NHS Choices:
Much of the time it is diagnosed clinically through examination and other tests.
Now, couldn't ME = Arthritis and within that you might have Rheumatoid Arthritis - if you see what I mean?
Will it be necessary to change from what we have now I wonder in terms of myalgic encephalopathy... Could you still have this as the label with sub-groups existing within?
What we view now as 'triggers' that are not always more than subjective assessments from patients: could still be a result of 'autoimmunity'. But any test may not demonstrate this specifically - we could still be dependent on symptom assessment and medical history.
Of course it all rather depends on the replication, and acceptance of Rituximab Trials and their results but also on the replication/improvement on Bansal's work as well as other related research that will need to take place I would imagine - disease mechanism work etc.
i wonder if the theory of a hit and run virus in cfs/me is the auto immune group as the immune system is still on and or over reacting but infection is cleared. While the antiviral responders( and ampligen) get hit with the virus and the immune system is supressed and infections are ongoing until treated?? With either one it seems as though treatment is going to be ongoing??
Hmm you make a good case: I wanted to move away from myalgic encephalomyelitis however I think myalgic encephalopathy could potentially act as a universal subheading similar to arthritis. Perhaps with the prefixs of autoimmune, chronic viral etc.
I personally suspect that may very well be the case! I think Prof. Edwards has discussed this over in the other thread, where the virus appears to be the trigger factor but the susceptibility to developing a seemingly autoimmune ME likely starts years in advance. The virus then serves to exploit this susceptibility, triggering the production of whatever autoantibodies and immune defects cause and perpetuate symptoms.
I think it is interesting that EBV is often the triggering virus and suspect it is due to its direct impact upon circulating B-cells making it more likely to trigger the chain reaction required for ME however any pathogen likely has the potential to trigger this.
I also suspect that the people responding to antivirals could well also fall into the autoimmune group but see effect from antivirals either due to the immuno-modulatory effects of the antivirals or through reducing the viral load every person harbors. As I discuss in the article it appears that people with ME do not have any pathogen not present in the general population but seem to start responding to them - possibly due to increased sensory sensitivity or a lowered immune response. It is interesting to note that the conception that autoimmunity is the immune system in overdrive - while this appears to be the case it is more an imbalance of immune response - with patients often having increased B-cell activity often at the loss of a degree of the innate response - as seen with the dysfunction of NK cells observed in ME. Certainly the entire immune system is interconnected and dysfunction in one area has many downstream effects upon other areas of the immune system.
I have to keep reminding myself that ME is not a single disease when discussing it though - for some these viral issues could be the causative problem but I think more research needs to be done on this.
With regards to the ongoing treatment I suspect that will likely come down to whether the disease process has long-lived plasma cells at its heart or shorter lived cycling plasma cells. Either way I think rituximab treatment 2-3 times a year is a lot more manageable than the regimes of antivirals such as valcyte that some doctors and patients use, but I look forward to seeing the OMI trial using both and whether this could have an effect!
I'm not seeing where ongoing use of Rituximab is a complete plus even if it may help in the short term. The list of adverse effects are somewhat chilling to contemplate.
I know beggars can't be choosers, but the more ideal solution -- in the case that at least some of our ME subgroups turn out to be at root autoimmune -- would be to figure out how to kick the body back out of that reaction cycle. As opposed to just hammering B cells back down every 4-6 months.
If the cause is short term cycling plasma cells then depleting all the B-cells could potentially break the loop. The trouble here lies with longer lived plasma cells perpetuating the illness and meaning the newly formed B-cells are also trained to produce the autoantibody which causes the relapse once levels return. Unfortunately I don't think we're at the point where we can break the loop in any other way - hence why nearly all autoimmune conditions are incurable but that's not to say they're un-treatable. I'm not trying to sell rituximab as a fix all treatment but it has certainly jump-started the research in a new, interesting direction and if it can also help some patients that's an added bonus!
We're dealing here with the benefits rituximab proposes as a treatment and as a research opportunity and I think from a personal perspective that both are positive however its benefit as a research opportunity has much further reaching consequences. I think it's a fair comment to make that ME research has been treading water for quite a few years and i'm hoping that if an autoimmune group can be identified it will benefit not only that group but will bring some much needed attention for the entire ME group.
I completely agree that some of the potential side effects are a little chilling but this is why trials are needed - to see whether the benefit outweighs the risk. I certainly cannot condone usage before this testing is done but that patients have already tried this off-label clearly speaks to the suffering that ME patients have to go through at times. Hopefully in the future better treatments will be developed but for this to happen the groundwork has to be there, and rituximab has the potential to lay some of that.
I hold the perhaps unpopular view that ME/CFS isn't a whole range of different diseases for the majority. I agree that there is some root immune fault/autoimmunity which ultimately is manifest in different ways as a result of various factors (infections, genetics, disease stage, etc.) and so treatment for the underlying immune/autoimmune root should result in improvement for the majority.
Either way, such research is very good to see and I like the fact the UK charities are contributing strongly.
Thanks Andrew a very good and interesting article. Look forward to more from you.
I too hold a similar view: I believe it was Prof. Edwards gave a breakdown of 60:20:10:4:2:1 or something similar with regards to causes, with the 60% block being autoimmunity and I can't help but feel he's on the money with this.
Well let's hope that independent replication endorses the emerging view of autoimmunity, because that's where ME research has fallen down in the past. We get 'interesting' initial studies usually of very small size and then little or no follow-through; but endless theory and often treatments being handed out for some on the back of it.
This time the difference has been the Norwegian Trial to date. What's missing I think is the autoimmunity research - the link that ties Rituximab as a treatment to ME. I am afraid that Bansal's work thus far for me wasn't very impressive: but I am hoping - sincerely - that they can replicate and improve upon it: taking it further and establishing this link.
Not sure how/if Lipkin and his Chronic Fatigue Initiative 'Pathogen Hunt' will impact on the notion of autoimmunity: hopefully it wont as presence of pathogens is not a precursor to this kind of disease.
Anyway, I'm still transcribing his broadcast so will learn some more about the immune disruption he did discover in due course I guess...
I can scarcely describe how bizarre it is to see references to the Tahoe outbreak as being of interest when no CFS researchers are interested in it.
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