Earlier this week we spoke to a journalist who had written a piece about chronic fatigue syndrome or M.E. for RNZ's online site The Wireless. We received a huge amount of feedback from sufferers and their families about their experiences with the debilitating illness.
Many sent in questions they wanted answers to, some hoping for treatment options. We decided to get an expert in to explain the illness a little more in depth.
Dr Ros Vallings has spent decades dedicated to helping those with CFS, she has a clinic in Howick and has taken a break from patients to respond to our listeners. 

Listen to radio interview here.

​ME Association Statement: Negative phase III clinical trial result from Norway for Rituximab in ME/CFS | 27 November 2017 


By Dr Charles Shepherd, Hon. Medical Adviser, ME Association.
“I was disappointed to learn – while at the Royal Society screening of the documentary, Unrest, in London last Thursday – of the preliminary (but unpublished) results from the phase III clinical trial of Rituximab, that has been carried out in Norway.
“This large, multicentre, ‘gold standard’ clinical trial, involved 152 people with ME/CFS receiving either Rituximab or a placebo, with initial treatment followed by maintenance treatments at 3, 6, 9 and 12 months, and a two year follow up.
“The ME Association has consistently taken the position that Rituximab could be one of the most promising developments in the search for a safe and effective drug treatment that is targeted at the underlying disease process in ME/CFS.
“We also know that the physicians involved in this research – Drs Oystein Fluge and Olav Mella from the Haukeland University Hospital in Norway – have taken great care in the way that they have devised the protocols for the clinical trials that have been carried out and reported.
“Despite the headline negative finding, we believe that this trial will still provide useful insights and contribute to a better understanding of M.E., and we also have the results from the Cyclophosphamide clinical trial to look forward to. We are very pleased that this knowledgeable, and valued, research team will continue with their work, trying to find answers to the M.E. puzzle.
“The ME Association Ramsay Research Fund had set aside around £60,000 to help support this research, or to help fund a clinical trial of Rituximab here in the UK, if such funding was required, and applied for by a reputable research or clinical trials group. No research grant applications have been received.
“It is difficult to comment further on these very basic preliminary results, and my understanding is that no further comment will be made by those involved until the study is published early next year. However, we do believe that it is correct and helpful for the patient community to be notified about the disappointing key conclusions prior to publication.
“Any decision – including if it is going to be sensible for the charity sector to be raising or spending further large sums of money on research involving the theoretical basis to this treatment (i.e. immune system dysfunction, involving the B-cell component of the body’s immune system), or further clinical trials to assess the safety and efficacy of Rituximab – will have to wait until more detailed information becomes available about the outcome of this phase III clinical trial, and the scientists involved have expressed their opinion as to whether further such research is justified.
“Based on the results from the clinical trials that have been published so far – along with the rather mixed evidence from people with M.E. who have been prescribed Rituximab outside formal clinical trials – it does appear that this type of immunotherapy could still be relevant to at least a sub-group.
“If it is agreed by experts in this area of immunotherapeutics (and we will be seeking expert advice), that we should continue to explore the role of Rituximab as a possible treatment for ME/CFS – and try to find immune system biomarkers that could help to identify the sub-group of people with M.E. who are most likely to respond to such treatment – the ME Association will continue to invite applications for research grants to the Ramsay Research Fund.
“Medical journals are less enthusiastic about publishing negative research findings or negative results from clinical trials. However, given the enormous amount of interest in Rituximab, from both people with M.E. and the medical community, I am confident that these results from Norway will be accepted for publication in due course.
“The ME Association is currently considering a number of other research applications – some of them quite large – and trustees will discuss the latest news about the Rituximab clinical trial at their Board meeting in December. A decision will then be made as to whether the £60,000 currently set aside, should remain as a ring-fenced sum for funding Rituximab research, or used for other biomedical research applications.”
Dr Charles Shepherd,
Hon Medical Adviser, ME Association.

The statement from Haukeland University, Bergen from Professor Mella is a major disappointment for people with ME and their families.
What had looked to be a promising line of research that could lead to an effective treatment for a subgroup of patients defined by the Canadian Criteria and major understanding of the pathology of this disease has proven to be inconclusive.
Naturally, at the charity, everyone is disappointed. We are disappointed for all the ME patients and carers and families and friends.
We are especially disappointed for all of our supporters and all who have made such generous and tireless efforts to raise funds and awareness of our campaign.
We are very disappointed also for the Haukeland research team - a wonderful team who have brought hope to all patients - and, importantly, brought new insight into this disease and new interest from other areas. 
However, we have found, throughout 12 years of trying to change the way that ME is perceived, researched and treated that it is never easy.
It would be easy to give up, to resign oneself to nothing changing, to accept the status quo.
But we think differently.
At the 2017 Colloquium/Conference we invited Karolinska Institutet in Stockholm to present negative results. Because it is important to use negative results for positive effects. Negative results are data and the Norwegian rituximab trial has generated a lot of data that needs to be looked at very carefully. 
When we first engaged Professor Jonathan Edwards into research into ME one of the earliest comments he made was that he was pleased to note that our conference did contain negative results.
We see the positives in this research which has been performed by researchers of the utmost integrity who have not made headlines for the sake of it but have thoroughly conducted outstanding research, and still retained a humility that is to their credit and that of their colleagues and team.
We have an excellent research team in Norway which has served the ME patient community and their families with honesty, integrity, professionalism, determination and an empathy which had never been seen before in this field.
We have established good working relationships between the Norwegian researchers and the UK Centre with input from UCL and UEA/Quadram Institute.
We have data now – more than before.
We have research which IiMER has established and a foundation for the Centre of Excellence for ME.
We have international collaboration in research into ME that will continue.
And we have new plans – already in the making.
The researchers from Haukeland will give more detail on their results and publish a paper or two which will benefit all studying ME. 


For us, we have invited the Haukeland team to Norwich to discuss the way forward.
We remain positive. Another setback, another day.
We have already been in discussion with our advisors and with the Norwegian team and we will meet to clarify the best way forward in the near future with our major funder and researchers.
We still have much good research being funded and being planned and feel our stategy is, and will pay off and lead to the most rapid route to finding cause(s) of ME and effective treatments.
In another age, and in another struggle which has some parallels to that which is forced upon people with ME, these words strike a chord -
“ We must accept finite disappointment, but never lose infinite hope. ” 
- Dr Martin Luther King

Source: http://www.investinme.org/IIMER-Newslet-1711-03.shtml

No Isolation for ME

November 15, 2017– 

With myalgic encephalomyelitis (ME), one of the most insidious consequences of this devastating and disabling disease that affects patients can be the isolation experienced.
This is especially true for younger patients and the consequences of this can extend far into adulthood and beyond and lead to unnecessary departure from society.
Already, due to the consequences of a lack of a sensible and standardised pathway to care, patients are stigmatised and excluded from society. 
This need not be so and much could be done to avoid this by tackling this issue early on for young children affected by ME. 

Earlier this year Invest in ME Research was contacted by a Norwegian company who were interested in demonstrating a product that was aimed at reducing the isolation experienced by many younger people who were unable to attend school, or were cut-off from social contact due to illness.
Obviously, the charity immediately saw the parallels with ME and the possibility of raising awareness of one of the least publicised side effects of this disease on patients, and their families.
Our immediate reaction was how we can help use this to publicise awareness of the effects of ME on children. 
We then invited the company – No Isolation – to take a table at our 12th International ME Conference in London (IIMEC12) and offered to work further to support this campaign.
The charity felt this to be a worthwhile cause that could help alleviate some of the unnecessary suffering that careless or ignorant education systems inflict on sick children and their families.
The company’s product - AV1 robot - helps children and youths with ME to continue to be connected to their peers at school despite not being present for all or some of the time due to illness.
The robot is now available in the UK and together, with No Isolation, we are hoping to set up trials.
Invest in ME Research will be contacting local education authorities to trial AV1.
Initially, a trial of three AV1 robots will be set up involving families who currently have a child with ME who is unable to attend school, or whose regular attendance is compromised by ME.
Children and youths with long-term illness such as ME do not need to be excluded from their friends’ activities and progress and schools have a responsibility not to ignore them – something which can lead to long term discrimination.
The robot, called AV1, acts as the students’ eyes, ears and voice in the classroom on days where they cannot be physically present. With AV1 the student controls the robot with an app on a tablet. When the student raises their hand, a light flashes on AV1’s head. The robot can be turned 360 degrees, so the student can see the entire classroom and talk to other students. If the student does not feel like actively participating, they communicate it by turning on a blue light on AV1’s head. AV1 is designed to withstand Childs play, and can join classmates in the playground or on after school visits.


AV1 is already helping ME-patients across Scandinavia, the Netherlands and UK.
Children and youths suffering from ME is the largest user group – a salient point and one that ought to be a red flag for any education system.
Research fellow Jorun Børsting and senior lecturer Alma Leora Culén at the Institute for Informatics, University of Oslo, are researching the technology needs of ME-patients. Having studied the use of AV1 among nine children and youths suffering from ME they see a big advantage in the fact that the robot is designed with ME-patients in mind. Børsting stresses that the robot cannot fully replace normal attendance at school or home teaching, but act as a supplement.

We invite support for this campaign to help younger children – in the hope and knowledge that it could lead to fewer problems in the future for young people affected by ME.
“Of the children I followed several had not attended school in a long time when they first received the robot. 
Some had been out of school for over six months. 
After they received AV1, all of them participated regularly, on their own terms” 
- Jorun Børsting, Research fellow and senior lecturer Alma Leora Culén at the Institute for Informatics, University of Oslo.


Invest in ME Research will receive no financial reward for this campaign. 
The charity does this in order to highlight and overcome a major consequence of becoming ill with ME.
We invite support for this initiative by assisting us with contact to local schools and education authorities.
The advantage in participating in class through a tablet is that they have full control over sound levels, light and movement. In a normal classroom they do not have the option to control sensory inputs in this way. Furthermore, they can participate exactly when they feel like it, taking into account that symptoms can fluctuate over the course of the illness, even from hour to hour


Invest in ME Research is a major UK charity which campaigns for biomedical research into ME and for proper education of healthcare staff and support for ME patients. 
The charity has been instrumental in initiating a UK Centre of Excellence for ME and there are now five PhD student positions involved in researching ME.
# # #
If you would like more information about this topic, please contact Invest in ME Research at 02380 643736 or email at info@investinme.org.
If you would like to be one of the families trialling AV1 and would be prepared to report back during the trial and work with us, No Isolation and the school/school authority then we would be very keen to hear from you.

The London Med Ed Workgroup is a new initiative formed during the 11th Invest in ME International ME Conference 2016 (IIMEC11), held in London on June 3, 2016.
Solve ME/CFS Initiative’s vice president for research and scientific programs, Dr. Zaher Nahle, was tasked by meeting organizers to assemble a starter team of Med Ed experts from conference participants to examine national and international medical educational efforts in ME/CFS and explore areas for potential collaboration.
The goals of the London Med Ed Workgroup are to 1) create effective vehicles for improving current medical information on ME/CFS, 2) improve the dissemination and exchange of medical information, and 3) develop educational materials building on existing tools and relevant literature.
On June 4, 2016, the team held its first meeting in London, followed by a teleconference in July. In addition to Dr. Nahle, the team thus far is comprised of several prominent patient advocates and ME/CFS experts including Mary Dimmock, Dr. Rosamund Vallings, Dr. James Baraniuk, and Dr. Vicky Whittemore. Regular updates will be provided on the work of this team as well as its ongoing efforts and expansion.
“This collaborative work is yet another way in which we are trying to create momentum on all fronts of ME/CFS,” said Dr. Nahle. “When it comes to a complex, poorly understood disease like this, it is critical that every medical health professional, all medical school curricula, and every governmental agency site is up to date and equipped with the right information and tool kits; this is feasible in this day and age.”
Notably, Dr. Nahle is also part of the CDC Technical Development Workgroup (TDW) that provides input on the accuracy and effectiveness of the CDC website and the dissemination of correct information to healthcare providers as well as the general public. There are many aspects of the current CDC website that provide insufficient or incorrect information to the public; we are actively engaged in working to correct this serious deficiency.
 
​

A Great Addition to the ME/CFS Field

Dr. Maureen Hanson has been all over the place in chronic fatigue syndrome (ME/CFS) lately.
Hailing from Duke and Harvard and now at Cornell she has quite a pedigree. With a family member with chronic fatigue syndrome (ME/CFS), she also has a personal stake in this disease, and has penned several editorials supporting ME/CFS research. Her "Be Aware and Beware" Huffington Post blog and her Congressional Hill post "When Hoofbeats are Zebras" showed that she's not afraid to leave the laboratory and get out and advocate. At every opportunity she makes it very clear that ME/CFS is a real disorder. Her last gut study went viral and was picked up by over 50 media outlets.

She recently spoke at the Invest in ME Conference, and at the Simmaron Patient event, and is on the scientific board of the Simmaron Research Foundation.

As and added bonus she appears to be very good at getting NIH grants. She first popped up in ME/CFS with a grant to study XMRV in 2011. Since 2011 she's gotten three R21 grants on ME/CFS, and is a collaborator on a big RO1 immune functioning grant with Fabian Campagne at Cornell. She's also being funded by the Hitchens Foundation's Chronic Fatigue Initiative. She seems to have a talent for taking on interesting studies. She's definitely someone to keep an eye on.

Metabolomics

Now she's moving into metabolomics. In the Solve ME/CFS webinar this week Hanson revealed that a small metabolomics study she pieced together using donations had replicated Naviaux's core finding - that ME/CFS is hypometabolic disorder.

Her study was smaller than Naviaux's: compare the 80 or so patients/controls and 612 metabolites measured in his study to the 32 patients/controls and 361 metabolites in the Hanson pilot study. All the participants n her study were also female and all came from an ME/CFS expert, Dr. Susan Levine, who has been collaborating heavily with Dr. Hanson.

Naviaux noted that the field is moving so quickly that it lacks standardization and this study showed it. The Hanson team used a different kind of mass spectrometer, and handled the samples differently. In fact, the way Hanson was talking, it sounded like everything was done differently in the Hanson study.

Nevertheless, Hanson's core findings were strikingly similar to Naviaux's. She found an almost across the board reduction in metabolite levels; fully eighty-eight percent of the metabolites in the ME/CFS patients were reduced (compared to 84% in Naviaux's study.)

Some similar pathways (phospholipids, purines, proline, fatty acid metabolism) showed up and others did not. The dramatic sphingolipid reductions Naviaux found, for instance, did not show up in the Hanson study, and Hanson found several pathways that did not show up in the Naviaux study.

Hanson suggested that the completely different methods used as well as the different geographic region the patients hailed from could explain the differences found. Whatever the differences found, the core finding of a distinct hypometabolism in chronic fatigue syndrome (ME/CFS) clearly excited Hanson and she stated:
"The similarities are very promising for metabolomics to give some very useful information about ME/CFS"
Click to expand...
Hanson's metabolomic money is gone, but she's applying for an NIH grant. Scoring a big ROI grant - say $3,000,000 over several years - would, of course, be a major step forward for metabolomic research in ME/CFS.

How to Fit Many Symptoms into One Core Pathology ...

With the Chronic Fatigue Initiative's help, Hanson has also been studying mitochondrial genetics. Naviaux has stated that people with ME/CFCS do not have a genetic mitochondrial disease, and Hanson's results backed that assertion up; in fact, none of the almost 200 patients tested had anything suggesting an inherited mitochondrial condition. She did, however, find evidence - as Ron Davis has suggested - that genetic polymorphisms could be producing different symptoms in different ME/CFS patients.

Maureen Hanson's Solve ME/CFS Initiative Webinar

One altered mitochondrial DNA gene, for instance, appeared to be associated with gut symptoms; another was correlated with chemical sensitivity - a problem that gets almost no research attention - but can be terribly impactful. (Dr. Naviaux believes, interestingly enough, that low energy states lend themselves to hypersensitivity reactions. )Hanson's study suggested genetic differences in the mitochondria could result in widely varying symptoms in ME/CFS. She noted though, that much, much larger studies are needed to validate her findings.

Hanson is not by any means done with the mitochondria; she is also examining the mitochondrial functioning of NK, T and B cells. The poor functioning of NK cells is one of the most consistently found immune abnormalities in ME/CFS, but problems with T-cell functioning have also been found, and reports of poorly functioning B-cells have shown up as well.

Could the immune problems in ME/CFS be caused by a hypo-metabolic or under-energized immune system? Hanson will use an Agilent device to determine if problems with glyoclysis - the energy pathway that releases ATP and ATP through the conversion of glucose - are sending immune cells into a somnolent state.

Hanson then went on talk about her recent gut findings which included a reduction (another reduction) in diversity and abundance of microbial species in ME/CFS. She also suggested that the reduction in microbial diversity seen in an ill twin might be associated with that twins reduced aerobic capacity.

A New Chronic Fatigue Syndrome (ME/CFS) Center

In some very good news Hanson announced that the Dean at Cornell has allowed Dr. Hanson to create a new ME/CFS research center called the "Center for Enervating NeuroImmune Disease" (CEND). (Enervating means feeling weak and lacking in energy). The Center will collaborate with Betsy Keller at Ithaca College. It contains three researchers, involves eight labs which have or are applying for an ME/CFS grant, and is working with no less than five physicians - and Hanson hopes it will grow significantly.

The fact that Hanson felt it was time to create a formal center for ME/CFS at Cornell, plus her ability to hit the ground running with a strong staff is very encouraging particularly at Cornell - which has a top ranked Medical School. The new Center will surely be a strong candidate for the projected NIH research consortium.

Maureen Hanson is clearly the kind of researcher we've been looking for and hope to get more of. She's very committed, she can get grants, she's daring enough to start an ME/CFS research center and she clearly works well with others.

Some ME/CFS Metabolomic / Metabolic Studies Coming Up

The Naviaux study really caught our attention but a surprising number of other groups are doing metabolomics/metabolic/mitochondrial studies. McGregor in Australia, for instance, has been studying metabolism/metabolomics in ME/CFS for years. Here are some metabolomic / mitochondrial studies underway.
o    Hanson's small ME/CFS metabolic study (under review now).
o    The Naviaux/Ron Davis OMF funded expansion of Naviaux's recent study
o    Naviaux's studycomparing the metabolome of ME/CFS patients and other diseases
o    Hanson's NK, T and B cell energy production study
o    The Lipkin/Hornig study tying metabolomics results in the blood to their gut findings.
o    The Bateman Horne Center/Watanabe Japanese metabolomics study. In what is clearly a Suzanne Vernon study, the Watanabe study, a Michael Hougton Canadian Cytokine Study, and Alan Light's Autoantibody study will all use the same 100 patients samples - thus allowing them potentially to merge their findings.....
o    Nath's metabolic chamber study in the Intramural study
o    Several studies from Armstrong and McGregor in Australia
o    The SolveME/CFS in house mitochondrial study (more on that later.)
The Bateman-Horne Study
Depression - Sometimes a Metabolic Disorder?

ME/CFS might not be the only disease which may get turned around by metabolomics. Let's take a quick look at a metabolomic study that could turn the medical profession's conception of depression - a disease that's often been confused with ME/CFS by doctors - upside down.

The potential breakthrough started, as many breakthroughs do, with one patient. As reported in the Pittsburg Post-Gazette, frustrated doctors who had run out of options with a treatment resistant young man with suicidal depression, turned to a biochemical geneticist for help.
The geneticist suggested doing a metabolic analysis of the young mans cerebral spinal fluid. That analysis turned the his life around. After finding that he had deficient levels of a protein called tetrahydrobiopterin, or BH4, they began treating him with a substance called sapropterin. He was able to recover, return to school and is now working in his chosen field.

After getting the same results in five other treatment resistant depressed patients, the group began a larger study looking at hundreds of metabolites in the spinal fluid of 33 patients. About two thirds of them displayed significant metabolic abnormalities; of those more than half (12/21) had the same cerebral folate deficiency found in the young man. All showed improvements including reductions in suicidal thoughts on a high dose regimen of folinic acid.

For some young people on the protocol the improvements have been dramatic. The parents of one 13 year stated that within a month of taking the folinic acid, “we felt like we had our Ben back."

This isn't to say that all the patients had that kind of result, but it does indicate the power of this technology to uncover new insights that can lead to dramatic improvements even in seemingly intractable diseases like treatment resistant depression (and who knows...perhaps ME/CFS.)

What would, one wonders, a metabolomic analysis of ME/CFS patients cerebral spinal fluid find?
 
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