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PHANU Rising II: Dr. Marshall-Gradisnuk Talks on Rituximab, Biomarkers and Chronic Fatigue Syndrome

PHANU is moving to a bigger, better laboratory at Griffith University

PHANU is rising.... Lead by Dr.Sonya Marshall-Gradisnuk and Dr. Donald Staines, the PHANU ME/CFS Australian research team presented more studies at the 2011 Ottawa IACFS/ME conference than any other, scored a major grant from the Mason Foundation, established close ties with Dr. Peterson at the Simmaron Foundation and is moving to a larger laboratory at Griffith University.

This team is moving....Despite being formed just three years ago, PHANU's co-leader, Dr. Staines provided the keynote speech on "New Directions for ME/CFS Research" and Dr. Marshall-Gradisnuk followed that up with a talk on Immunological Biomarkers at the 2011 Invest in ME conference.

Earlier this year Phoenix Rising got to talk with Dr. Marshall-Gradisnuk. The interview revealed a 'quietly confident' and careful researcher.

Background


] Dr. Marshall-Gradisnuk's PHANU research team lit up the Ottawa IACFS/ME Conference

We really appreciate any researcher that takes on chronic fatigue syndrome and you are now deeply immersed in it. You’ve done a lot of work on exercise physiology and the effects of hormones on exercise and the immune system. In retrospect it seems like you would be a good fit for a group of patients with poor exercise ability, poor natural killer cell functioning and hormonal issues. How did you get started with this disorder?

Our collaboration between Bond University and Queensland Health grew from a joint interest in neuroimmunology and public health. In particular there are a number of conditions of public health importance which possibly have a neuroinflammatory or neuroimmune basis. Hence our research interest.

We expect to grow to include not only ME/CFS but perhaps multiple sclerosis, Parkinson’s disease and disorders of ageing. As you have noted it builds upon our strengths in exercise physiology, immunology and public health. (Since this interview was done PHANU has been moving to a bigger lab space in Griffith University)

Rituximab and Autoimmunity in Chronic Fatigue Syndrome


PHANU researchers have long been interested in autoimmunity in ME/CFS and hope to do a Rituximab study

When you accepted the Mason Foundation grant you stated that it would allow you to conduct a Rituximab pilot study. Is that a done deal?

Again this research is in early days. Having only just been notified of this grant there is now much to be done by way of planning and implementing the research programme. We are hoping to link in with other researchers on the Rituximab issue to implement this research as soon as possible. We can’t say for sure at this stage how long it will take.

We know that Rituximab works in many auto-immune diseases and cancer but that it’s also a very powerful drug and, of course, ME/CFS appears to be heterogeneous condition. Dr. Peterson is excited about the drug but he’s also warned that some people with ME/CFS may need their B-cells. If you are doing a pilot trial will you be trying to uncover what types of patients Rituximab works in?

This will be for the study design. We don’t have the fine details on this question yet, however we are finalizing this in the coming months.

Except for yourself and Dr. Staines, not much attention has been given to the potential autoimmune aspects of ME/CFS. In a series of papers over the past few several years you’ve proposed that an autoimmune reaction to the neuropeptides that effect the integrity of the blood/brain barrier might be present in CFS and other disorders. If this enticing theory is true it could account for neuro-inflammation and/or neurodegeneration in a host of ‘neuropsychiatric disorders’ such as multiple sclerosis, Parkinson’s disease, ALS and ME/CFS. Unless I’m wrong, though, work hasn’t been done yet to prove or disprove its efficacy in ME/CFS has it?

As you say this is an enticing theory but still only a theory. Our task is to link researchers with skills in all these areas who may not have worked together before in ME/CFS. Autoimmunity probably has a role in the conditions you mention.

Unfortunately it has not been a prominent part of ME/CFS research except for our group at Bond University. However as awareness of this possibility gradually expands, supported by our research findings, we believe research funding institutions will not wish to neglect developing scientific evidence that ME/CFS may in fact be an autoimmune disorder.

The other side of the coin is that CBT and GET, which we have always been opposed to in ME/CFS, may be shown to have no place in a proper medical scientific approach to ME/CFS diagnosis and treatment.

Will you be using your grant monies to take a deeper look at this theory?

Yes, that is correct.

In one paper you suggest that phosphodiesterase inhibitors such as the ‘antidepressant’ Rolipram which has been found to have anti-inflammatory and immune modulating factors as well. Have it or any other PDE4 inhibitors been tried in ME/CFS to your knowledge?

We are not aware PDEIs have been tried in ME/CFS before. However PDEIs have been proposed by us in several publications. We urge caution, though, as these drugs are potent and have side-effects. Be clear that we are not recommending them because they may have anti-depressant effects. It just so happens these drugs may, for theoretical reasons, be useful in ME/CFS. ME/CFS is not a psychiatric disorder and no inference should be drawn from the rationale for using PDEI's.

Ottawa IACFS/ME ME/CFS Conference

PHANU has focused a great deal of attentions on natural killer and T-cells (natural killer cell receptor pictured)

The 2011 Ottawa conference was really a breakout conference for PHANU. You submitted more abstracts and presentations than any other group and some of your preliminary findings – altered immune functioning after vaccination, altered purinergic functioning, altered gene expression during pregnancy, altered miRNA levels in natural killer cells – and others were fascinating.

Thank you for the acknowledgement and it was a great regret that I could not attend, however PHANU was very well represented. Our group has worked very hard in the past three years to get to where are today. I am very proud to lead a very talented group of researchers and clinicians as well as have significant funding support from the Alison Hunter Memorial Foundation as well as the QLD Government and Mason Foundation.

Our research has been always been focused on the potential neuroimmune mechanisms and autoimmunity through assessing the cellular and molecular mechanisms in CFS/ME.

At the Ottawa conference Dr. Klimas called PHANU’s finding of reduced cytotoxic T-cell functioning a ‘gold star’ study and said it was a significant advance. If you can prove reduced perforin levels and functioning in cytotoxic T-cells as well as natural killer cells, how would that change things?

I feel very honoured that Professor Klimas stated this at the conference. My approach is to always approach research and outcomes very carefully and in terms of these results it may have indicated a further marker for CFS/ME.

Dr. Peterson and Simmaron

Dr. Peterson was a co-author of several PHANU studies at the Ottawa IACFS/ME conference. How did PHANU in Australia hook up with a Nevada physician/researcher?

I along with the CFS/ME research group that I lead have the greatest respect for Dr Peterson, He is a true gentleman and an amazing clinician. I met Dr Peterson when he came to Bond University in December 2010 when he was invited to an International Science Symposium for CFS/ME that I was leading with Dr Staines from Queensland Health.

Our meeting was organized by the Alison Hunter Memorial Foundation - a wonderful group of dedicated people. I am very proud to say that Dr Peterson is a significant collaborator on a number of large national grants for CFS/ME that I have.

Biomarker for CFS

You stated “Ultimately our aim is to develop a clear diagnostic test for CFS and establish a national testing facility here at Bond University, which we believe could happen within five years”. A biomarker, of course, kind of like the holy grail for ME/CFS; lots of people have tried (and are trying) yet we still don’t have one. Regarding PHANU’s ability to find a clear diagnostic in five years would you say you are hopeful, cautiously optimistic, quite optimistic or feel pretty sure it will happen).

Quietly confident

Could we have a biomarker right now and not know it? Something that has been identified but not fully validated?

Probably not. It will be important to truly understand the pathomechanisms of ME/CFS before anyone can be 100% confident in a biomarker.

Research

The preliminary results from PHANU's pregnancy study suggests estrogen could play a role in neuro-immune issues in chronic fatigue syndrome

Phanu also presented a fascinating study focusing on gene expression during pregnancy in chronic fatigue syndrome patients at the Ottawa Conference. The study was prompted by two observations: (1) that some women with CFS temporarily get better in the midst of their pregnancy and (2) that women with autoimmune disorders such as multiple sclerosis often experience the same pattern. Preliminary results from the study suggested that the normal gene expression patterns found in pregnancy may not occur in pregnant women with ME/CFS.

This is a fascinating much under-investigated area in ME/CFS area given the gender predominance in CFS and it goes nicely with a CDC story showing strikingly high rates of women with CFS with heavy rates of bleeding, premenstrual problems and other gynecologic abnormalities including disturbing high rates of hysterectomies. Can you tell what these studies may mean?

Yes, these studies provide significant insight into the possible neuroimmune mechanism that may possibly underlie CFS/ME. Moreover, the predominance of CFS/ME in females and the associated symptoms that have been documented may be possibly explained by oestrogen having pleotropic effects on the immune system.

It has been shown that exposure to oestrogens stimulates antibody production but decreases T-cell mediated delayed-type hypersensitivity (DTH), granulocyte-mediated inflammation and natural killer (NK)-cell mediated cytotoxicity. The heightened antibody response, while decreased immune function, suggests as we have thought for many years, the neuroimmune influences on CFS/ME.

Preliminary results from a PHANU blood and spinal fluid study suggested that neuropeptides involved with a central nervous signaling pathway called the purinergic system were abnormal in ME/CFS patients.

This system showed up in neon lights in the Light gene expression studies. The purinergic receptors they found play a role in several areas of interest in CFS including immune regulation, the smooth muscles lining the blood vessels (think blood volume), pain sensitization in the immune cells in the spinal cord/ brain, and in sympathetic nervous system functioning. Can you comment on this finding?

Further evidence on the role of the purinergic system is also required. The purinergic system has a significant influence over T cell functioning and neurotransmitter roles such as in neuropathic pain. Generally this supports the notion that neruoimmune mechanisms may underlie CFS/ME

You’ve done quite a bit of research on the effect hormones have on the immune system and on exercise. There do appear to be hormonal irregularities in ME/CFS but they appear to be mostly mild. Do you think problems with hormones such as cortisol, norepinephrine, epinephrine will play a major role in the immune dysfunctions found or in the problems with exercise?

This is a very complex question. At this stage we would simply suggest there may be disorders of neurotransmitter metabolism that we will better understand when the pathomechanisms are known. These disorders are likely to be exacerbated by exercise. We do not support exercise testing in ME/CFS patients; however, our understanding of exercise physiology and biochemistry has been a significant strength for us.

(eds. note - neurotransmitters are a big focus in chronic pain disorders such as fibromyalgia, IBS, TMD, etc.)

Your exercise study with healthy people suggested that increased stress hormone production (norepinephrine, epinephrine and cortisol) after exercise tends to reduce natural killer, cytotoxic T-cell and B-cell levels and that NK cell levels were knocked down for over 24 hours. Given the problems with NK (and now T-cell functioning) levels in ME/CFS and the exercise issue this is an intriguing finding.

Yes, it is true these studies provide a very good insight into the possible neuro-immune interactions following a stressed induced activity such as exercise. CFS/ME patients may not be ideally applied for a blanket method intervention, however, due to the number of CFS/ME sub groups.

The biphasic response of total lymphocytes numbers may be due to circulating stress hormones, including epinephrine, norepinephrine, and cortisol. It has been suggested that catecholamines induce the initial increase in lymphocyte numbers, whereas cortisol induces lymphopenia after exercise. This exercise induced immunoregulation of the endocrine system on lymphocytes is seen in lymphocytes including CD8+ T-cells and NK cells.

Further evidence on effects on catecholamine metabolism is required along with evidence of a possible disorder of the cholinergic system.

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[/quote]View the Post on the Blog
 
Thanks very much, Cort,

I've been waiting for this post. Griffith University isn't too far away so it's possible to imagine flying up there for a day or two to be involved in any tests or treatments, if only they'd open them up for older people over 50!

In the meantime, there are a host of new ideas in this interview to try to get my head around!

regards, Lynne
 
Lots of interesting stuff here. Thanks again for another great article, Cort!

I was interested in the comment that they don't support exercise testing in PWME. I've been concerned about the use of the Lights' type of exercise test as a potential diagnostic in case it produces serious relapses - I'm not sure if that's what's meant in this article.

Wouldn't it be great to get some scientific data to squash CBT/GET? It really does violence to us.

Very hopeful.

Was there some call for funding for them recently? Matching funding or something? Or have I just made that up in my head?
 
Thanks very much, Cort,

I've been waiting for this post. Griffith University isn't too far away so it's possible to imagine flying up there for a day or two to be involved in any tests or treatments, if only they'd open them up for older people over 50!

In the meantime, there are a host of new ideas in this interview to try to get my head around!

regards, Lynne
Thanks Lynne, it certainly looks like an exciting time for PHANU. I liked Dr. Marshall-Gradisnuk's statement that she was quietly confident a biomarker was in reach :) as well as all the neuro-immune connections the research was providing....
 
Lots of interesting stuff here. Thanks again for another great article, Cort!

I was interested in the comment that they don't support exercise testing in PWME. I've been concerned about the use of the Lights' type of exercise test as a potential diagnostic in case it produces serious relapses - I'm not sure if that's what's meant in this article.

Wouldn't it be great to get some scientific data to squash CBT/GET? It really does violence to us.

Very hopeful.

Was there some call for funding for them recently? Matching funding or something? Or have I just made that up in my head?
I was a bit surprised by the exercise statement as well. Dr. Marshall-Gradisnuk, of course, is trained in exercise physiology - so she has alot of background there. On the other hand, quite a few researchers and physicians employ the test. Dr. Peterson, Staci Stevens at the Pacific Fatigue Lab, Dr. Klimas, Dr. Kogelnik - all use the test to document treatment effectiveness, of course, disability and its being used in research studies..Of course it does place a burden on patients and will certainly lead to some sort of relapse in just about everybody :).

The Light's test is an unusual; I recently talked to Dr. Kogelnik and he said they don't use it because they believe its too harsh....

Simmaron has called for funding to complete a joint Simmaron/PHANU project that will enable PHANU to make full use of the $800,000 plus grant they recently received from Mason...I'm not aware of other calls for funding.
 
"It will be important to truly understand the pathomechanisms of ME/CFS before anyone can be 100% confident in a biomarker." This is an important statement, and reflects the difference beteen science and pseudoscience. Even with potential markers they are careful. Many have wondered why the biomedical researchers have not attacked CBT/GET more forcefully. One reason is they are waiting for accumulated evidence, and do not wish to present opinion in advance of the science.

The complete lack of biomarkers or even good diagnostic testing protocols doesn't seem to stop CBT/GET proponents from making almost unqualified supporting statements about the efficacy of CBT/GET. That is a hallmark of pseudoscience.

Bye, Alex
 
Lots of interesting stuff here. Thanks again for another great article, Cort!

I was interested in the comment that they don't support exercise testing in PWME. I've been concerned about the use of the Lights' type of exercise test as a potential diagnostic in case it produces serious relapses - I'm not sure if that's what's meant in this article.

Wouldn't it be great to get some scientific data to squash CBT/GET? It really does violence to us.

Very hopeful.

Was there some call for funding for them recently? Matching funding or something? Or have I just made that up in my head?
Yes, there is apparently an urgent need to raise money for the first phase of the large study that the Mason Foundation will then progress to fund. I recently made a donation at the Simmaron website – I hope many of us can contribute!

From Rich Carson’s Appeal For Funds for the Simmaron/PHANU project:
"The Mason Foundation in Australia believes in this research so much, it has dedicated $830,000 to fund the second part of what is the largest-ever collaborative international ME/CFS project. But with one caveat: phase I of the study must first be funded.
Patients have already raised the first $87,000 of the $225,000 needed to complete phase I, thanks in particular to the kind generosity of Linda Tannenbaum of the Neuro-Immune Disease Alliance, Inc. and to your recent donations. Patients and our loved ones are the heroes after all. But we are still short $138,000.

That means $830,000 in possible ME/CFS research is up for grabs. All we need to do is raise $138,000 more to get it. We can’t count on the government. But we can count on ourselves to do what is right, and we can count on support from our family and loved ones. "
http://www.prohealth.com/library/showarticle.cfm?libid=17164

Donate here:
http://simmaronresearch.com/donate/
 
Also, there was this call for help for funding:

From Invest in ME FB page:

Our Australian researchers need our help to continue their research. Their recent presentation at Invest in ME ( London 2012) was very impressive. They deserve our support:

Alison Hunter Memorial Foundation
announces
Fundraising for Flow Cytometer Cost AUS$200,000 Funds raised to date
Aus$24,000
Griffith University
School of Medical Science
Griffith Health Institute

Population Health and Neuroimmunology Unit (PHANU)
Steering Committee
Chair Ross Humphreys
Professor Sonya Marshall Gradisnik PhD
Associate Professor (Adjunct)Don Staines MBBS MPH
Professor (Adjunct)Daniel Peterson MD
Christine Hunter AM

The focus of PHANU is to investigate the pathomechanism of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to develop novel biomarkers for the early diagnosis of the
illness. Under the leadership of Professors Marshall-Gradisnik and Staines, PHANU works in close collaboration with Daniel Peterson MD Chief Investigator/Clinician of Simmaron Neuroimmune Research Foundation Nevada USA.

PHANU is seeking to obtain a new flow cytometer to continue their immunological and genetic investigations.This equipment upgrade is critical for their ongoing ME/CFS research programme examining spinal fluid and blood and will allow more advanced analyisis of possible pathomechanisms. A Donation Form can be accessed at www.ahmf.org via Donation tab.
Donations can be posted to
Alison Hunter Memorial Foundation
PO BOX 6132
North Sydney NSW 2059
Australia
or alternatively faxed to 0011 61 2 9958 6285.

Your help to fast track this purchase would be greatly appreciated.
Chris Hunter AM

http://www.ahmf.org/
 
Lots of interesting stuff here. Thanks again for another great article, Cort!

I was interested in the comment that they don't support exercise testing in PWME. I've been concerned about the use of the Lights' type of exercise test as a potential diagnostic in case it produces serious relapses - I'm not sure if that's what's meant in this article.

Wouldn't it be great to get some scientific data to squash CBT/GET? It really does violence to us.

Very hopeful.

Was there some call for funding for them recently? Matching funding or something? Or have I just made that up in my head?
I was a bit surprised by the exercise statement as well. Dr. Marshall-Gradisnuk, of course, is trained in exercise physiology - so she has alot of background there. On the other hand, quite a few researchers and physicians employ the test. Dr. Peterson, Staci Stevens at the Pacific Fatigue Lab, Dr. Klimas, Dr. Kogelnik - all use the test to document treatment effectiveness, of course, disability and its being used in research studies..Of course it does place a burden on patients and will certainly lead to some sort of relapse in just about everybody :).

The Light's test is an unusual; I recently talked to Dr. Kogelnik and he said they don't use it because they believe its too harsh....

Simmaron has called for funding to complete a joint Simmaron/PHANU project that will enable PHANU to make full use of the $800,000 plus grant they recently received from Mason...I'm not aware of other calls for funding.
Cort, any chance that you could get back to Dr. Marshall-Gradisnuk and ask more about her stance on exercise testing? Does PHANU not support it for any use, not even in research studies? (must be valuable to have the Stevens-Snell results and the Light results for the understanding of the pathophysiology of ME/CFS, I'm thinking?) What are her/their reasoning here? Would be so interesting to know more.

Also, do you know from which date they'll be installed at Griffith? Is it at their Logan campus? (I'm in Sweden, but Brisbane, QLD, is my second home - or was when I could still travel...)

As always, thanks for a great post!
 
I hope to talk with her about the exercise testing...

From my eyes on the ground - Bob Miller - who's been there; Bond gave them a great lab but Griffith made them an offer they couldn't refuse; they appear to be kind of a hot item in Queensland :)cool:). The Griffith lab is really good - more sophisticated than the WPI one - which was quite good - so its a great move for them. I did the interview awhile ago- from what I've gathered from anecdotal reports is that they're either in or just about in to the Griffith site...Not sure of the exact location except that it is in a new wing that's close to the hospital.
 
A very intriguing interview, not least the attention to changes in pregnancy. As someone who 17 years into the illness had her first of 2 pregnancies (the second swiftly following the first.. though not designed that way ;) !!) and after severe hyperemesis had a very pronounced improvement which was maintained for almost 18 months post parturition I'm impressed that someone of SMG's calibre is at last looking at this. I suppose it's a logical step if you're going to treat ME as a possible autoimmune illness (I have had positive ANAs for many years at different points in my long ME history). What I'd hope the team might consider is the effect pregnancy might then have on women with ME in the long term. I revelled in the (almost but not quite 100%) improvement I had for those months in parts of my pregnancies and after the second, but since that time my ME has become much worse generally. I became housebound when my youngest first started school and that situation has not changed..has only become worse. Looking back I see the first 17 years as being very difficult, but 'cycling' in remissions and relapses where no remission met the quality of that attained in pregnancy but where, at times, I could pretend (almost) that I was 'functioning' as part of society, even if it was at a very low level. Since then, and my son turns 25 on Saturday, I have had a consistently downward trajectory and as I meet menopause I have also met my very worst symptom thus far: severe neuropathic pain of the skin which is horrific. It seems to me that the upheaval of pregnancy somehow creates changes which fundamentally change the terrain of the ME-ridden body, and not for the better. I do hope PHANU continue to look at this aspect in greater detail, not least as it may inform more generally.
 
A very intriguing interview, not least the attention to changes in pregnancy. As someone who 17 years into the illness had her first of 2 pregnancies (the second swiftly following the first.. though not designed that way ;) !!) and after severe hyperemesis had a very pronounced improvement which was maintained for almost 18 months post parturition I'm impressed that someone of SMG's calibre is at last looking at this. I suppose it's a logical step if you're going to treat ME as a possible autoimmune illness (I have had positive ANAs for many years at different points in my long ME history). What I'd hope the team might consider is the effect pregnancy might then have on women with ME in the long term. I revelled in the (almost but not quite 100%) improvement I had for those months in parts of my pregnancies and after the second, but since that time my ME has become much worse generally. I became housebound when my youngest first started school and that situation has not changed..has only become worse. Looking back I see the first 17 years as being very difficult, but 'cycling' in remissions and relapses where no remission met the quality of that attained in pregnancy but where, at times, I could pretend (almost) that I was 'functioning' as part of society, even if it was at a very low level. Since then, and my son turns 25 on Saturday, I have had a consistently downward trajectory and as I meet menopause I have also met my very worst symptom thus far: severe neuropathic pain of the skin which is horrific. It seems to me that the upheaval of pregnancy somehow creates changes which fundamentally change the terrain of the ME-ridden body, and not for the better. I do hope PHANU continue to look at this aspect in greater detail, not least as it may inform more generally.

Cort: I wonder if you are able to ask SMG more about this aspect of her research. And if she ever wants any blood from a UK longtimer, then feel free to offer that too :thumbsup:
 
A very intriguing interview, not least the attention to changes in pregnancy. As someone who 17 years into the illness had her first of 2 pregnancies (the second swiftly following the first.. though not designed that way ;) !!) and after severe hyperemesis had a very pronounced improvement which was maintained for almost 18 months post parturition I'm impressed that someone of SMG's calibre is at last looking at this.

I suppose it's a logical step if you're going to treat ME as a possible autoimmune illness (I have had positive ANAs for many years at different points in my long ME history). What I'd hope the team might consider is the effect pregnancy might then have on women with ME in the long term. I revelled in the (almost but not quite 100%) improvement I had for those months in parts of my pregnancies and after the second, but since that time my ME has become much worse generally. I became housebound when my youngest first started school and that situation has not changed..has only become worse.

Looking back I see the first 17 years as being very difficult, but 'cycling' in remissions and relapses where no remission met the quality of that attained in pregnancy but where, at times, I could pretend (almost) that I was 'functioning' as part of society, even if it was at a very low level. Since then, and my son turns 25 on Saturday, I have had a consistently downward trajectory and as I meet menopause I have also met my very worst symptom thus far: severe neuropathic pain of the skin which is horrific.

It seems to me that the upheaval of pregnancy somehow creates changes which fundamentally change the terrain of the ME-ridden body, and not for the better. I do hope PHANU continue to look at this aspect in greater detail, not least as it may inform more generally.

My goodness lilpink - that is really rough - particularly the severe neuropathic pain in the skin...

The CDC, by the way, did a fascinating presentation on a study in Ottawa that showed greatly increased (and I mean GREATLY increased) gynelogical problems in women with ME/CFS. I'm going to get that out shortly (in a review of the Chronic Overlapping Pain Disorders workshop). I think its a fascinating area in ME/CFS; it has been little explored but there's great potential..All ME/CFS's 'cousins' - FM, IBS, IC, TMJ, etc. strike significantly more women than men...

That upswing during pregnancy is fascinating....and then there's the potential downswing as well. We'll do a survey on this at some point. I'm going to try to get some docs to give us some ideas what to do during menopause as well.

I will try to talk to her more about this as well as the exercise question...
 
My goodness lilpink - that is really rough - particularly the severe neuropathic pain in the skin...

The CDC, by the way, did a fascinating presentation on a study in Ottawa that showed greatly increased (and I mean GREATLY increased) gynelogical problems in women with ME/CFS. I'm going to get that out shortly (in a review of the Chronic Overlapping Pain Disorders workshop). I think its a fascinating area in ME/CFS; it has been little explored but there's great potential..All ME/CFS's 'cousins' - FM, IBS, IC, TMJ, etc. strike significantly more women than men...

That upswing during pregnancy is fascinating....and then there's the potential downswing as well. We'll do a survey on this at some point. I'm going to try to get some docs to give us some ideas what to do during menopause as well.

I will try to talk to her more about this as well as the exercise question...
Thanks Cort. I look forward to you posting the CDC presentation, not least as it's heartening to hear of the possibility that they have looked at part of this illness with some seriousness at last. I do find it curious that in my own case I avoided much pain, and certainly neuro pain, until almost 42 years of illness had passed. I do wonder if the concomitant hormonal upheaval has been to blame in some way (though I also had a severe allergy prior to and overlapping with the development of the pain, where no allergy had existed before..and I wonder if that too could have been hormonally driven in some way).

The menopause question is a tricky one. Because of my pregnancy improvements I had elected to try HRT back in 1998. The effects weren't dire (until I was removed from it at the end of the 'experiment' without tapering) but they weren't positive either. A second tranche of HRT back in 2004 (this time with the addition of testosterone), and not really elected by me..more of a 'twisted arm' whilst in the grip of a very bad crash indeed, was deliterious, so hormone replacement doesn't seem to necessarily be the opiton of choice for women with ME. My gut feeling is that there is little a menopausal woman with ME can do other than 'grin and bear it' and hope that the natural settling of hormones allows the body to calm down and be less reactive and fragile as time passes. I personally feel that immune modulation, as a treatment for the underlying ME would also make the passge throguh menopause much easier. I feel that in discovering that supplementation of female hormones was not beneficial for ME suggests that it is the immune component of pregnancy which is the driver of substantial improvement during that time, that in combination with the increase in blood volume which I suspect has implications for perfusion of the brainstem?
 
the good thing is that PHANU is going to be connected to the new Gold Coast university hospital which moves/opens next year. Basically its a training hospital for medical staff. If treatments occurr or not maybe the new bread of docs coming through will get some education on cfs and the current docs may think twice when thinking about cfs instead of writting it off as a psych problem. Maybe if they look into it further they will see the research showing all the immune dysfunction going on. Hopefully it inspires docs to treat cfs patients more seriously and use treatments that are available now like antivirals etc which many docs just wont even consider. As it becomes more mainstream, hopefully many of these treatments will be covered by our health system instead of us having to pay off label prices. Imagine paying $33 for a valcyte script instead of $3000, makes these types of treatments more available to us cfsers in australia and hopefully a flow on affect to other countries.

cheers!!!
 
I would just like to suggest that referring to ME/CFS as a neuroimmune or neuroendocrineimmune disorder implies that the basic problem lies in the nervous system, the endocrine system and the immune system. I think this is misleading. It's true that many of the symptoms in ME/CFS are associated with dysfunction in these three systems. In addition, there are other symptoms that are associated with the skeletal and heart muscles and with the digestive system.

But I maintain that the basic problem is not in any of these individual systems and organs as they are usually compartmentalized for study. Rather, the dysfunctions in all these organs and systems stems from a common cause, which is more fundamental. That common cause is in the basic biochemistry, which affects all these organs and systems. It's the vicious circle that includes glutathione depletion, a functional B12 deficiency, a partial block in the methylation cycle, loss of folates from the cells, and draining of the sulfur metabolism.

This is the essence of the pathophysiology, in my view, and the dysfunctions in all the above systems and organs stem from it. It explains why this disorder is chronic. It explains the oxidative stress. It explains the mitochondrial dysfunction. It explains why certain other vital organs are not seriously impacted, including the liver, kidneys and pancreas. It explains the leading candidate for being a biomarker, i.e. the lowered activity of the NK cells, which is due to low perforin production, in turn due to glutathione depletion in the NK cells. It explains why the gene expression for perforin was observed to be higher than normal, while the amount of perforin produced was found to be lower than normal.

So far, the GD-MCB hypothesis appears to be able to explain the published research results in ME/CFS, and treatment based on it is reported by many PWMEs to be helping them.

I have shared my views with the PHANU group. I wish them success in their ongoing research effort.

Best regards,

Rich
 
I would just like to suggest that referring to ME/CFS as a neuroimmune or neuroendocrineimmune disorder implies that the basic problem lies in the nervous system, the endocrine system and the immune system. I think this is misleading. It's true that many of the symptoms in ME/CFS are associated with dysfunction in these three systems. In addition, there are other symptoms that are associated with the skeletal and heart muscles and with the digestive system.

But I maintain that the basic problem is not in any of these individual systems and organs as they are usually compartmentalized for study. Rather, the dysfunctions in all these organs and systems stems from a common cause, which is more fundamental. That common cause is in the basic biochemistry, which affects all these organs and systems. It's the vicious circle that includes glutathione depletion, a functional B12 deficiency, a partial block in the methylation cycle, loss of folates from the cells, and draining of the sulfur metabolism.

This is the essence of the pathophysiology, in my view, and the dysfunctions in all the above systems and organs stem from it. It explains why this disorder is chronic. It explains the oxidative stress. It explains the mitochondrial dysfunction. It explains why certain other vital organs are not seriously impacted, including the liver, kidneys and pancreas. It explains the leading candidate for being a biomarker, i.e. the lowered activity of the NK cells, which is due to low perforin production, in turn due to glutathione depletion in the NK cells. It explains why the gene expression for perforin was observed to be higher than normal, while the amount of perforin produced was found to be lower than normal.

So far, the GD-MCB hypothesis appears to be able to explain the published research results in ME/CFS, and treatment based on it is reported by many PWMEs to be helping them.

I have shared my views with the PHANU group. I wish them success in their ongoing research effort.

Best regards,

Rich

I just dont think i can agree with you on treating the partial methylation block as the answer. It may be helpful but we just arent seeing the improvements or cures from this treatment like we do from other treatments like ampligen, antivirals and ritux. To me i think this shows that treating the infections or immune dysfunction is closer to the cause then treating methylation with b12,folates etc

At the end of the day i dont think anyone treatment is going to do the full job, i thinks its going to be a combination of things tailored to individuals dysfunctions.

cheers!!!
 
Hi, Heaps.

I agree that treating the partial methylation cycle block is not the whole answer for most PWMEs. As I see it, this treatment addresses the core of the pathophysiology, but it does not directly address the etiologies (root causes) or the toxins and pathogens that may have accumulated during the illness. It can help with these, because it restores the function of the immune system and the detoxication system, but if the toxic load is too high, the detox system is not able to take care of it on its own, and there are many ways that various pathogens can hide from the immune system or foil it, so they may need to be dealt with directly, also. I agree that positive results seen in some cases with Ampligen, antivirals, Rituximab, LDN and the various forms of MAF are clues suggesting that the above is true. I also suspect that many PWMEs have congenital immune deficiencies that made them vulnerable to various infections. These may include IgG subclass deficiencies and mannose binding lectin deficiency, among others.

Best regards,

Rich
 
the good thing is that PHANU is going to be connected to the new Gold Coast university hospital which moves/opens next year. Basically its a training hospital for medical staff. If treatments occurr or not maybe the new bread of docs coming through will get some education on cfs and the current docs may think twice when thinking about cfs instead of writting it off as a psych problem. Maybe if they look into it further they will see the research showing all the immune dysfunction going on. Hopefully it inspires docs to treat cfs patients more seriously and use treatments that are available now like antivirals etc which many docs just wont even consider. As it becomes more mainstream, hopefully many of these treatments will be covered by our health system instead of us having to pay off label prices. Imagine paying $33 for a valcyte script instead of $3000, makes these types of treatments more available to us cfsers in australia and hopefully a flow on affect to other countries.

cheers!!!
Great news about PHANU being connected with hospital training. It appears that these Australian Universities and hospitals are intriguing by their work; they had a good thing in Bond (far better it appears than the lukewarm support Dr. Klimas got from Univ of Miami) and now Griffith gave them a better offer....That's progress :)