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How does Rituximab relate to other ME research?

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Andrew Gladman explores the current research climate of ME/CFS, discussing how existing research ties into the emerging autoimmune hypothesis.


Link: 'New data reveal first predictive biomarkers to tailor rheumatoid arthritis therapy'
Image: computer generated image of an antibody

Throughout the history of ME it is safe to say that understanding of the condition and the research itself has been somewhat fractured at best and lacking significance in many areas. In the last 30 years, following the Lake Tahoe outbreak which piqued the interest of doctors and media, little progress seems to have been made in terms of physiological understanding of the disease processes involved, perhaps due to the stigma of ME as a purely psychological entity which is only in recent years being shaken off.

This struggle clearly speaks to both the complexity of the illness in general and the misunderstanding that many researchers and doctors still have of it to this day. The causal theories proposed range from chronic viral infections, mycotoxins, stress, psychological stress, immune dysfunction and many more; yet none of these have been shown to adequately represent the patient population as a whole or to account for the presented symptoms and varying degrees of disability.

The fractured and inadequate biomedical research to date has left the majority of patients with treatments such as Graded Exercise Therapy (GET) and Cognitive Behavioural Therapy (CBT) as recommended by the National Institute of Health and Care Excellence (NICE). However, the heavily promoted PACE Trial - which endorses these treatments - has itself come in for a large amount of criticism with regard to various aspects of its design, data management and conclusions: and is seen by many patients as being unrepresentative of their own experiences.

This leaves the only other option for patients as specific symptom relief, which many GPs are still unwilling to prescribe; alternative psychological treatments, such as the Lightening Process and Mickel Therapy - coming with a costly price-tag and no guarantee of success; and off-label treatments such as Valcyte or Ampligen, which while of anecdotal benefit to some, are not yet approved for use, and can attract another heavy cost and the risk of quite serious side effects.


A positive change in momentum

Despite this we do seem to be witnessing a positive change in momentum for ME research and in terms of official recognition that ME has a physiological foundation. In 2011 the Medical Research Council (MRC) announced that more than £1.6m was specifically available for biomedical research into ME/CFS - funds that have now been allocated to specific projects. Alongside this came the establishment of the CFS/ME Expert Group chaired by Prof. Stephen Holgate with the aim of exploring new ways in which to encourage research into ME/CFS; while in America, the Chronic Fatigue Initiative has been pivotal in encouraging collaboration between researchers in many different areas and trying to raise awareness of ME.

Prof. Holgate's Expert Group has undoubtedly helped with the establishment of multiple initiatives including the UK CFS/ME Research Collaborative (UK CMRC) in April this year, and as a joint charity initiative we have seen the forming of an ME Biobank at University College London - which received a welcome boost from the US National Institutes of Health recently. The annual Invest in ME International ME (ME/CFS) Conference is at the forefront of this momentum change, meaning there are now more opportunities to present and showcase the latest research from new and experienced ME scientists from across the world. Other than something of a misfire in the form of XMRV, the growing research community seems to be going from strength to strength, despite the slow action of other groups such as the US Centres for Disease Control and Prevention (CDC).


Professor Olav Mella (left) and Dr Oystein Fluge

Undoubtedly one of the most recognised presences in recent years at the Invest in ME conference has been the Norwegian Doctors Oystein Fluge and Olav Mella. In 2009 Fluge and Mella’s Rituximab pilot study seemed to show major transient improvement for all 3 patients and in doing so attracted quite a lot of attention. A follow up study published in 2011 built upon this, showing further transient improvement rates of 67% in a double-blind placebo controlled study. These results created a clear buzz in the ME community and with data from the maintenance trial of Rituximab presented at the 2013 IiME Conference and due for publication soon - promising positive results gained by extending the treatments over a longer period and aimed at maintaining improvement - it is clear that Rituximab is one of the most positive developments in ME research for decades. Positive, not only as a potential treatment for some, but also as a breakthrough in understanding of the physiological cause of ME: implying as it does that autoimmunity may lie at the root of the illness.

XMRV has taught us not to get carried away before the data is published and reliably replicated, but it’s clear that these studies are incredibly important going forwards - with the potential to change the way researchers and doctors alike approach ME. The importance of these further studies is underlined by the impressive response some of the Norwegian pilot study patients experienced. When asked how they were doing 4 years after the pilot study took place, one of the patients said, “Right now I'm living an active, normal life as a full time student and I really appreciate that the doctors at Haukeland gave me the chance and the health to do what I want in my life, I will never take this lifestyle for granted!” Considering she has received no further Rituximab treatments, it is clear that this drug has a lot of potential!


Autoimmune theory and other research findings

One important question that the autoimmune theory does raise is how all the other research findings tie in with it. There are numerous researchers currently looking into a plethora of different aspects of ME and it is important to give each one careful consideration. Each area has the potential to represent one piece of a very complex puzzle and only once each is weighed against the others can we discover where each piece goes and indeed whether the piece we are looking at is even a part of the overall puzzle.


Standford ME/CFS Initiative Research Team
Dr Jose Montoya (bottom right) Professor of Medicine in the Division of Infectious Diseases

For example, Montoya and the Stanford ME/CFS Initiative (Summer 2013 Update), and the projects from Lipkin and Hornig, are looking in detail at the presence and prevalence of pathogen involvement in ME. Given the historical and current causal theories posited by pathogen involvement, many patients and doctors are looking forward to the results once they are published.

It is perhaps difficult to make the initial connection of pathogens to an autoimmune theory and it is of note that many of the pathogens commonly identified or associated with ME are prevalent in similar numbers within the general population. Therefore the question may be why the immune system suddenly starts to respond to them, and becomes a compounding problem for ME patients.

This logically leads to further questions as to whether these pathogens are re-activating and hence require an ongoing immune response or whether the immune system is over-responding to otherwise inert pathogens. Perhaps this could point to an important part of the underlying disease mechanism whereby the immune system is overreacting to the mediators released by the chronic low level pathogens everyone harbours – although as yet these theories are speculative. Another answer could come in the form of dysregulated sensory gating. A recent study in Japan (Health Rising Article by Marco) discusses the possibility of troublesome sensory gating in ME at some length, specifically the potential for this to explain the sensory overload many patients experience. 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.

Another researcher undertaking ground-breaking work in the ME field is Professor Julia Newton. Her studies looking into the muscle dysfunction along with the effect of lactic acid upon these muscles and the effect of low blood pressure in ME patients are areas that have not received much research attention in recent times. However both represent intriguing possibilities for physiological problems in ME, possibly even pointing towards the vascular system as a potential autoimmune target bringing with it possible direction for treatment – this is one of the reasons why her results promise to make some very interesting reading. This is one area of research however where the link with autoimmunity would appear to be more subtle – for this reason it is all the more exciting that Professor Newton has been looking into Rituximab herself.


Dr Amolak Bansal Chief Scientific Advisor
ME Solutions

Of all the links between different research areas and the effects of rituximab, Dr. Amolak Bansal’s work into B-cells represents one of the strongest: as would be expected considering the B-cell depleting action of rituximab. Published in March 2013, his research was aimed at intensive B-cell immunophenotyping in order to identify whether there were any consistent B-cell abnormalities in the general ME/CFS population. It is very interesting to note that this study came about as a direct response to positive results shown in rituximab trials – underlining the importance of the rituximab trial in shaping new research directions. Prior to this study the research literature on the topic of B-cells in ME, like many areas of ME research, was inconsistent and sparse. The results of this study however led Dr. Bansal and his team to conclude that there was perhaps a “subtle tendency to autoimmunity.”

Of all the research mentioned, this has the clearest link to the autoimmune theory and its importance is underlined by the desire of Professor Jonathan Edwards and the team at UCL to undertake a similar trial as a preliminary stage of their planned UK rituximab trial – a preliminary trial that thanks to the fundraising efforts of Invest in ME is able to begin in the near future. Professor Edwards, in a recent interview with Phoenix Rising, explained that one of the primary aims of a UK rituximab trial would be to connect the data from the Norwegian study with the B-cell abnormalities Dr. Bansal has reported.

The immune dysfunction hypothesis is nothing new in ME/CFS, being proposed numerous times throughout the history of the disease – certainly the signs have always been there that the problem may stem from the immune system. Many of the drugs patients use off label such as Ampligen and Imunovir act primarily through modulation of the immune system and its aberrant responses, while drugs such as Valcyte act through antiviral properties but still exhibit an immunomodulatory effect. There are many reports of patients improving on these drugs and it’s difficult to not encounter the remnants of the outrage many patients feel towards the denial of Ampligen approval numerous times over the years.

Valcyte itself has been heralded many times by patient subgroups as a treatment that has helped them turn the corner. However a recent study by Kogelnik and Montoya has had disappointing results – perhaps the antiviral properties help a sub-group for whom chronic viral infections are a major factor but these results do not confirm many patients' beliefs that viruses are to blame. The results simply do not appear as positive as many hoped for. There is the possibility that immunomodulation might explain the improvement in patients for whom the proposed autoimmunity may be the problem, however more research will be required to confirm or deny this. The multi-armed trial involving both Valcyte and rituximab, proposed by Dr. Kogelnik and OMI-MERIT, could be the best way to determine whether Valcyte has a role as an ME treatment.


Future UK Rituximab trials

Of all the changes Rituximab and the autoimmune theory can and have been making, the most striking is likely the discussion and thought it has provoked among researchers, doctors and patients the world over - influencing the way researchers consider new trials and how patients view the future of ME. Many organisations have taken note of this through public declarations, and the ME Association in the UK have pledged both their interest in this emerging research area and a not insignificant sum towards a UK trial.


Dr Charles Shepherd
Honorary Medical Adviser
ME Association

Dr. Charles Shepherd has made many comments regarding Rituximab and has partaken in online question-and-answer discussions on the topic. The ME Association issued the following statement early in July for example, "we have consistently maintained that the positive results from the initial case study reports indicate that Rituximab could form a very significant development in finding a drug aimed at treating the underlying disease process in at least a sub-group of people with ME/CFS". While Dr. Shepherd had this to say regarding the autoimmune hypothesis: "I'm not yet convinced that ME/CFS is what doctors term an autoimmune disease. This is because from what we know so far there is no consistent and robust evidence relating to autoimmunity in ME/CFS that links specific autoantibodies and autoimmune tissue/organ damage or functional change to actual symptoms."

Dr. Shepherd went on to explain that a "wide range of immune system abnormalities have been reported in ME/CFS. These include the presence of low levels of autoantibodies in some people", and concludes that "a sub-group of people with ME/CFS have what I think is best described as an autoimmune component". Dr. Shepherd has also made it clear that the ME Association is very much in favour of supporting a UK rituximab trial proposal from a financial standpoint, provided that such a proposal meets the standard peer review process required by the Ramsay Research Fund.


Conclusion

It is clear then that research into ME seems to have made a positive turn, with more unique directions than ever and many initiatives to help researchers and patients alike. Certainly there is still work to be done in interpreting how evidence such as muscle fatiguability possibly due to excessive lactate build up, Post-Exertional Malaise and mitochondrial dysfunction fit into the puzzle; but now the evidence of physiological abnormalities is mounting, the interpretation and conclusions can begin to be made.

In Rituximab there is not only the offer of a potential treatment even if only for some, but also evidence for an autoimmune causation which could form the central trunk in the tree of ME research for the next few years, and from which all other areas could form the varying branches. The importance of Rituximab research in ME is clear from the comments of researchers, doctors and charities alike. With a phase III multicentre trial now close to being fully funded in Norway and due to commence early next year; plans in place for a smaller replication and exploratory trial at University College London; and early plans for further trials in America at the Open Medical Institute: it is clear that this development is being taken seriously.

It is important to remember that we are still likely dealing with multiple diseases under one larger heading as Prof. Stephen Holgate has outlined on numerous occasions. Rituximab is unlikely to help everyone with ME, however initial trials are incredibly positive and imply that for perhaps a significant sub-group, autoimmunity may be the causal disease mechanism. And it is not beyond the realms of possibility that there may be several different autoimmune conditions under the heading of ME/CFS.

If an autoimmune group can be identified within the larger ME/CFS group in the future, there is a strong possibility that this autoimmune group would be removed from the ME/CFS label and identified as a unique autoimmune entity. This group would likely be given a new name more befitting of the clinical findings. This could benefit those remaining in the ME/CFS group by removing those suffering from an autoimmune disease and allowing more relevant research to continue. Undoubtedly the research going forward has a direction that has been lacking in the past and with this, the potential for new treatments in the near future must surely follow. Who knows where we could be in another 5 years!


Further reading

Recent article by Sasha for Phoenix Rising exploring the history and future of Rituximab research in ME/CFS

Phoenix Rising thread in which Professor Jonathan Edwards is answering questions relating to a UK rituximab trial



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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!
 
"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.
 
If an autoimmune group can be identified within the larger ME/CFS group in the future, there is a strong possibility that this autoimmune group would be removed from the ME/CFS label and identified as a unique autoimmune entity. This group would likely be given a new name more befitting of the clinical findings. This could benefit those remaining in the ME/CFS group by removing those suffering from an autoimmune disease and allowing more relevant research to continue. Undoubtedly the research going forward has a direction that has been lacking in the past and with this, the potential for new treatments in the near future must surely follow. Who knows where we could be in another 5 years!

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 :)
 
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: is there really a need to assign those people 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?
 
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.
 
...It seems so simple to think but it's difficult to explain!

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:

Rheumatoid factor

This blood test checks to see if a specific antibody, known as the rheumatoid factor, is present in your blood. This antibody is present in eight out of 10 people with rheumatoid arthritis. However, it cannot always be detected in the early stages of the condition. The antibody is also found in one in 20 people who do not have rheumatoid arthritis, so this test cannot confirm rheumatoid arthritis. If it is negative, another antibody test (for anti-CCP) may be done, which is more specific for the disease.

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.

Interesting times :)
 
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??
 
Oh yeah it is :)
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.

Interesting times :)


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 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??

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.

http://en.wikipedia.org/wiki/Rituximab#Adverse_events

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.
 
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.

http://en.wikipedia.org/wiki/Rituximab#Adverse_events

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 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.
 
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...