Invest in ME/Prof Jonathan Edwards statement on UK Rituximab trial, 30 July

[Sasha]

A possible good biomarker in ME is low nk function, this also occurs in some other auto immune illnesses. Griffith uni in australia have found that its low bright cell nk function that is low in ME patients. I did hear a rumor that they were going to do a study with other auto immune illnesses with low nk function, MS and RA from memory and compare nk function as well as bright and dim cell nk function so they can possibly nail down a diagnostic biomarker for ME.

If one looks at the job of nk cells, i think it would be quite common to have issues with ongoing viral infections as its the job of nk cells to control these infections. Horse or the cart scenario too if its the infections keeping us ill or some type of auto immune issue or combination??

Are there immune drugs used to increase NK cell function? Do you know if these have been tried on PWME?

 

[Jonathan Edwards]

how interesting... in ME you have the Rituximab data....also... so you might be looking at a bone marrow link also? You want to do any speculation yet?

Not really. Bone marrow is where B cells are born and go to make antibody but the similarity between joint tissue and bone marrow relates to the mechanism of inflammation that happens to be triggered by RA antibodies. In thyroid disease the antibodies go for the thyroid, although they are made in bone marrow.

 

[Jonathan Edwards]

There are all sorts of immunomodulatory drugs that people have tried over the years and some people do seem to have a good response though there are very few trials. Even with the antivirals I've seen suggestions that these work by their immunomodulatory properties rather than their direct antiviral action (I've seen this said about Valcyte for HHV-6). If ME (at least for some people, and in roughly the proportion found by Fluge & Mella) is a B-cell, autoimmune issue, is it likely that these drugs are indirectly addressing that issue even when they've been assumed to be acting on other elements of the immune system or on particular viruses?

I am not sure i can get a feel for what's going on there. Sorry.

 

[Sasha]

I am not sure i can get a feel for what's going on there. Sorry.

Fair enough!

In RA, before Rituximab, were immune system drugs being used with any good effects? If so, is it likely that they were also targetting B-cells, or that some other mechanism was going on?

 

[Legendrew]

One thing I haven't seen discussed here much is the stomach issues many ME/CFS people suffer with - from reading//experience I know that it ranges from GERD type symptoms through IBS type cramping and a whole host of other things and most see this improve during times of remission and get worse during bad days and/or relapses. I sometimes see it attributed to diet etc but I was intrigued to read that several other autoimmune diseases of the nervous system such as MS also causes patients stomach symptoms. Does this come from the autoimmune process under/over-stimulating the autonomic nervous system? From reading I recall that the Vagus nerve is the nerve which connects the central and enteric nervous system and as a sensory nerve the ''attack'' on this would relate to Fluge and Mella's initial theory that ME could be an autoimmune disease of the sensory nervous system.

I'd be interested to hear what you have to think of this @Jonathan Edwards. Do you agree with what Fluge and Mella initially proposed or are you thinking the problem could lie within the central nervous system or elsewhere?

 

[cornwall13]

Just a quick question for Professor Jonathan Edwards, if possible, I was given imunovir by my specialist a few years ago and had really good improvements while on the drug ( I have some great graphs comparing my health before the drug and after) I am unfortunately not allowed to take it now because he has retired. he explained that imunovir alters the balance of the immune system. Would rituximab potentially do the same the same as imunovir and try and balance out the immune system?
Regards

 

[heapsreal]

Are there immune drugs used to increase NK cell function? Do you know if these have been tried on PWME?

interferon and interferon inducers can help increase nk function. ampligen in the most famous interferon inducers for cfs/me, the others are like immunovir. In russia there are quite a few, one which i have used with some success called cycloferon.

I think fixing the nk function can definately help treat the role of infections, as for the role of autoimmunity i dont know. It may turn out to just be a biomarker but there are a few doctors actively trying to improve nk function with some success in the patients symptoms??

 

[heapsreal]

I am not sure i can get a feel for what's going on there. Sorry.

Just a thought but maybe drugs like valcyte work through its mechanisms/side effetcs of bone marrow supression as neutropenia is a common side effect of valcyte??

 

[lansbergen]

Just a thought but maybe drugs like valcyte work through its mechanisms/side effetcs of bone marrow supression as neutropenia is a common side effect of valcyte??

And levamisole can cause agranulocytosis,

 

[ukxmrv]

Just a quick question for Professor Jonathan Edwards, if possible, I was given imunovir by my specialist a few years ago and had really good improvements while on the drug ( I have some great graphs comparing my health before the drug and after) I am unfortunately not allowed to take it now because he has retired. he explained that imunovir alters the balance of the immune system. Would rituximab potentially do the same the same as imunovir and try and balance out the immune system?
Regards

Here's one paper on Imunovir

http://www.cfids-cab.org/cfs-inform/Antiviral/diaz-mitoma.etal03.txt

Clinical Improvement in Chronic Fatigue Syndrome Is Associated with
Enhanced Natural Killer Cell-Mediated Cytotoxicity:
The Results of a Pilot Study with Isoprinosine®

And Prof Pinching did a pilot study but was refused further funding (I've spoken to him about this). Dolphin posted this to another thread and I've yet to find if it was ever published

http://www.mecfsforums.com/index.php?topic=4454.0

Findings: Some degree of clinical improvement (reduced symptoms, increased sustainable activity or both) occurred in 30% (definite) or 52% (definite plus probable), typical (in 90%) some months after the courses, lasting some months;
84% of retreated responders responded again. The commonest side effects were an increase in CFS symptoms during the course affecting some 41%. In those with such side effects, lower dose courses (0.5 gr. Tds for 2 months) were better tolerated but comparably effective.

(I'm one of the lucky patients who does well on this drug. Was able to receive an NHS prescription for a while but this was refused with the NICE guideline used as an excuse by my PCT)

 

[froufox]

Ive tried Imunovir too like ukxmrv and I experienced benefits from it quite quickly, so i guess that at least in my case, that would not suggest the same effect on B cells as Rituximab, and that it was due to some other mechanism. Didnt Dr Cheney say that it is supposed to balance the Th1 & Th2 arms of the immune system, in the direction of Th1?

Another thing that is supposed to work similarly to Rituximab in its regulation/suppression of T cells & B cell is LDN (low dose naltrexone), via the opioid growth factor and those people who do benefit from it, say that it can take a few months to get the full benefits. So perhaps the suppression of cell proliferation is one reason why they start to feel a bit better after several months? Unfortunately i know that some people cant even tolerate that, even at tiny doses. In my case it helped in the short term but not long term.

Here are some papers on opioid growth factor, T cells & B cells.

http://www.ncbi.nlm.nih.gov/pubmed/20598772

http://www.ncbi.nlm.nih.gov/pubmed/20965606

http://www.ncbi.nlm.nih.gov/pubmed/21807817

 

[Bob]

I also know an ME patient who is taking Imunovir, with success. And Nancy Klimas, a well-known ME specialist clinician in the US, uses it at her clinic, and says it is helpful. But I don't think she's published any trial results. It doesn't look like there's much published data for Imunovir for CFS.

Prof Pinching did a pilot study but was refused further funding (I've spoken to him about this). Dolphin posted this to another thread and I've yet to find if it was ever published

http://www.mecfsforums.com/index.php?topic=4454.0

This is the direct link to Dolphin's post of the abstract:
http://www.mecfsforums.com/index.ph...PHPSESSID=ss6a6vntbn65p8aa50amc2l454#msg48261

(My understanding is also that this research was refused funding and effectively 'shut down' in the UK.)

And this looks like a published paper for a similar pilot study in Canada:
http://informahealthcare.com/doi/abs/10.1300/j092v11n02_06

 

[MeSci]

Talking about bacteria and infections I find that for over 30 years and especially since crashing in 2000 I can go down very quickly with a throat infection that gives me identical symptoms every time. Nothing changes except maybe the extent of the burning I get in my throat.

One of the main symptoms that alerts me to the fact I am going to need antibiotics is that I get horrible strong muscle pains which shoot around my body. Normally I don’t have a lot of muscle pain only a bit at the end of a walk and nothing like what I experience when I need the antibiotics. As well as these very strong shooting muscle pains I also start feeling very unwell and have severe lack of energy and just have to lie around and do nothing feeling very depressed. I might also experience dizzy spells and have a need to sleep a few times in the day which I don’t normally have to do.

What surprises me is how quickly the infection starts and how quickly I can feel so very ill and also I don’t understand how the symptoms are identical every time. Once about 30 years ago my then GP swabbed my throat but I was told nothing grew and I didn’t need antibiotics yet I never get better unless I have them, my immune system just cannot fight this. However once I get started on the antibiotics I start to feel human again within 48 hours although of course it’s a few more days before I could say I feel really much better.

Does this type of problem/response relate in any way to an autoimmune problem I wonder? I don't understand how it would fit the theory.

Pam

I've fallen behind again on this thread as the alerts keep not appearing for it!

I would say that all your symptoms sound like post-exertional malaise. If you are sure that they only disappear when you have antibiotics, perhaps the specific antibiotics you take are most active against acid-forming gut bacteria, which could reduce the vicious cycle of over-exertion leading to muscle acidosis leading to hyperlactaemia leading to gut acidosis and (hypothesised and with some evidence) increased gut wall permeability perpetuating an autoimmune process, although just reducing 'bad' gut bacteria would make you feel better.

Alternatively, it could be coincidental with the fact that when you have taken antibiotics you have also paced your activities better and therefore recovered more quickly from whatever over-exertion may have led to the symptoms.

It's worth bearing in mind a saying relating to the common cold which goes something like:

If you don't take antibiotics, a cold will last about a week.
If you take antibiotics it will last about 7 days.

The same applies to an awful lot of illnesses including infections!

 

[MeSci]

Yes I'd really like to understand this more too...I get the basic gist of autoimmunity as that is what it sort of feels like a lot of the time (body attacking itself), but I cant get my head around die-off reactions/herxes (eg feeling poisoned, more fatigued etc) that Ive personally experienced with antibiotics, as well as many other pathogen killers that ive tried that don't have any immunomodulatory properties as far as i know (eg olive leaf), followed by very clear improvements (even if not a cure), if we dont have any more active pathogens than a regular person. Thanks for any more thoughts.

It's well known that antibiotics commonly cause side-effects, notably upsetting digestion, and a lot else follows from this. There info about antibiotic side-effects here.

As for effects from antibiotics and antivirals sometimes being good and sometimes bad, perhaps it is due to effects on gut flora. An antibiotic may preferentially kill 'good' or 'bad' gut bacteria. An antiviral might perhaps kill bacteriophages/phages - viruses which kill bacteria. If it kills phages that kill good bacteria, you will presumably feel better as the good bacteria increase. If it kills phages that kill bad bacteria, then the bad bacteria will increase and you will feel worse.

Here's some stuff about gut phages.

Hypothetical on my part but involves known mechanisms.

 

[Firestormm]

I also know an ME patient who is taking Imunovir, with success. And Nancy Klimas, a well-known ME specialist clinician in the US, uses it at her clinic, and says it is helpful. But I don't think she's published any trial results.



This is the direct link to Dolphin's post of the abstract:
http://www.mecfsforums.com/index.ph...PHPSESSID=ss6a6vntbn65p8aa50amc2l454#msg48261


My understanding is also that this research was refused funding and effectively 'shut down' in the UK.

Try this one also Mr Bob and an interesting wee chart here

 

[MeSci]

Try this one also Mr Bob and an interesting wee chart here

Can't see any reference to wee in that chart! I had to produce wee charts for the docs once. It was damned hard work. They ignored them.

Interesting that the only diet referred to is 'low sugar low yeast'. Nothing about leaky gut diet/gluten-free/low grain/dairy-free. If I was into conspiracy theories and even more enthusiastic about such diets than I am (is that possible?!) I would claim that it is because they are so successful they would put everything else in the shade. Ditto l-glutamine, sodium bicarbonate, alpha lipoic acid, zinc...

 

[Sasha]

I'm sorry, I seem to have derailed this thread a bit by asking about how drugs other than Rituximab might have an action on B-cells on PWME and we've gone a bit off-topic, perhaps, into the wider realm of those other treatments...

Shall we resume with our regular programme?

 

[Bob]

Jonathan Edwards - I'm not the only one on these forums to have had a severe initial illness (several years bedbound) and then a substantial, spontaneous remission for some years (working full-time, going to the gym, full social life, though with many short episodes of ill health) and then a big relapse (mostly housebound now).


I'm wondering how/whether the mechanism you're considering for B-cells allows for such remissions occurring spontaneously? Many people with ME do of course undergo gradual improvement without treatment, even if not to full health. I understand in broad terms your suggestion about how randomness might operate in setting up the disease but not in how the body might fix that on its own.

The autoimmune cycle mechanism can readily cope with spontaneous remission. The cycle can theoretically 'burn itself out'. This is not easy to explain in detail but for instance, it might happen if the cycle depended on antibodies binding not too weakly but not too strongly. Too weak might not cycle. Too strong might engage a control mechanism. Cycling may cause the binding strength to drift up and down (a bit like global warming and ice ages may be) but might also lead to the cycle spinning itself out of existence.

What I find much harder to explain is how you can have a long period of remission and then a crash. I am not sure I know of autoimmune diseases that do that - anyone got ideas? RA can remit and relapse and so can lupus but it usually seems more of a fluctuation of degree I think. There are models within the approach that could work but I am intrigued by this.

Sasha, do you think that spontaneous remission is very common? I've not knowingly come across anyone else who has experienced that pattern of illness. But very early on, when I first became ill, my symptoms fluctuated wildly, and I did have a very short period where I felt well enough to go back to work, and then a fast crash. (I wouldn't call it a remission, but the symptoms were negligible for a day or two.)

Jonathan Edwards, I experienced complete remission with hypo-thyroidism. And now, two years later, after my recent ME relapse, it seems that I have suddenly developed hyper-thyroidism. (Most recent blood test results not in yet.)

 

[Sasha]

Sasha, do you think that spontaneous remission is very common? I've not knowingly come across anyone else who has experienced that pattern of illness. But very early on, when I first became ill, my symptoms fluctuated wildly, and I did have a very short period where I felt well enough to go back to work, and then a fast crash. (I wouldn't call it a remission, but the symptoms were negligible for a day or two.)

I think we just don't have good data on this.

 

[Jill]

I've found both immunovir and LDN helpful. Immunovir became unavailable here in NZ, but I think you can buy it over the net now.
A doctor here in NZ, gives an injection of naltrexone. If it helps , he puts people on LDN. The help it gives is global - head, pain, fatigue - all goes. I have no idea why.

When something has helped me, it has helped EVERYTHING . ( that is what I mean by globally).

I too have always wondered why, as soon as one area of body starts going down hill, then I get back gut symtoms. Its as if there is like a snowballing cascade going on. My crashes are three days still, irregardless of all the meds that help, the meds stop helping once the crash begins. I've always described it like a faulty switched has turned. This has been the consistent pattern now for 30 years.