Mitochondrial muscle research and ME/CFS (Karl Morten et al, University of Oxford)

[charles shepherd]

Mitochondrial muscle research in ME/CFS

You tube video of Dr Karl Morten's presentation at the John Radcliffe (teaching) Hospital, Oxford last week (part of our ME Awareness Week coverage on 11th May) on what mitochondria do (very easy to understand) and the new research study into mitochondrial dysfunction in ME/CFS that is being funded by the MEA Ramsay Research Fund

You tube video:

Link to paper on viral infection and mitochondrial dysfunction that was referred to by Karl:
http://www.ncbi.nlm.nih.gov/pubmed/25642965

From the abstract:
"Furthermore, we demonstrate that herpesviruses induce mtDNA stress, which enhances antiviral signalling and type I interferon responses during infection. Our results further demonstrate that mitochondria are central participants in innate immunity, identify mtDNA stress as a cell-intrinsic trigger of antiviral signalling and suggest that cellular monitoring of mtDNA homeostasis cooperates with canonical virus sensing mechanisms to fully engage antiviral innate immunity."


This meeting, which also included the film 'Forgotten Plague' was organised and paid for by the ME Association and OMEGA

The MEA Ramsay Research Fund is the major funder of mitochondrial function research and is funding/has been funding 4 separate studies involving research into mitochondrial dysfunction at:

1 The University of Liverpool (Prof Anne McArdle et al): Abnormalities in Mitochondrial Function in Skeletal Muscle

Employing new technology, this research aims to demonstrate that skeletal muscle mitochondria are dysfunctional and cause the muscle fatigue experienced in ME/CFS:

‘The dysfunctional mitochondria then activate a process which leads to a chronic, low grade inflammation, commonly reported in patients with CFS, which in turn results in further mitochondrial abnormalities and the establishment of a vicious circle of events. Understanding the processes by which muscle fatigue occurs will lead to optimal interventions that break this vicious circle and improve muscle function and wellbeing of individuals.’

Extract taken from: MRC CFS/ME Current Projects

Preliminary results from the study were published in a recent paper: ‘The Role of Cytokines in Muscle Fatigue in Patients with Chronic Fatigue Syndrome’, The FASEB Journal, April 2015.

The authors recruited 100 untreated patients with CFS and 100 age and sex matched healthy controls, and concluded:

‘…a sub-group of patients with CFS may have low level inflammation and analyses are underway to further characterise other inflammatory markers in serum and muscle of these patients and to determine whether such changes could affect indices of muscle function or central fatigue.’

Lead researcher: Professor Anne McArdle

This research is being jointly funded with the Medical Research Council

RRF investment = £30,000


The University of Newcastle:

2 Dr Sarah Jayne Boulton et al: Comparison of results from a commercial and NHS blood test to assess mitochondrial function
This study will be comparing the results of a commercial blood test for mitochondrial function that has been developed by Dr Sarah Myhill and colleagues with the results from an international and widely accepted test of mitochondrial function which has a long and successful track record in clinical diagnosis and research of muscle disease particularly in the UK.

The aim is to determine the efficacy of each set of tests in relation to ME/CFS. In the exciting case that a synergy between the two diagnostic approaches exists, it is hoped that this preliminary study will promote an investigation into a more inclusive and highly resolved analytical technique for metabolic testing of people with ME/CFS.

Lead researcher: Dr Sarah Jayne Boulton

RRF investment = £21,305

MEA website info: http://www.meassociation.org.uk/201...-further-mitochondrial-research-20-july-2015/

3 Dr Joanna Elson: Patterns of Mitochondrial DNA Variation
This is an 18-month study that began in May 2014 and seeks to determine if patterns of mitochondrial DNA variation in ME/CFS are different than in healthy controls.

At the launch of the initiative, Dr Joanna Elson commented:

“Mitochondria are the powerhouses of the cell, and mitochondrial DNA provides the codes for proteins that are essential for energy production. We want to see if patients with ME/CFS have different patterns of mitochondrial DNA variation that could affect a person’s chances of succumbing to ME/CFS, or act as a barrier to recovery.”

Lead researcher: Dr Joanna Elson

This research is being funded by Action for M.E.

RRF donation = £5,000



Dr Charles Shepherd
Hon Medical Adviser, MEA

 

[Research 1st]

Why are the MRC still refusing to research actual ME patients, rather than those with Chronic Fatigue?
You could say the answer is obvious, it's the MRC who funded the PACE trial, so that's why.

However, I would like to this Science doesn't always remain twisted.

So please can someone tell me, what's the point at looking at CFS patients who have LOW Cytokine inflammation only and then referring this to a study on ME - when ME is associated to HIGH levels of inflammation?

Is that good quality science? or is it political?

ME means Inflammation of the brain/spinal cord, muscles.

By selecting people with FATIGUE and calling them 'ME' patients, this isn't accurate scientifically or medically.
So why is this still happening? Wrong heterogenous fatigue cohort = no cause of ME ever found.

Who benefits from this? People with Fatigue (yes) or people with Neurological ME (no).

Maybe oneday, someone might like to actually research people with ME (HIGH Inflammation) rather than Chronic Fatigue. If they do,we might get somewhere.

At least Ron Davis over in the USA knows what he's doing, and Dr Montoya who actively research people with ME (ironically then calling it 'CFS').

 

[charles shepherd]

MEA website version:

http://www.meassociation.org.uk/201...ondrial-muscle-research-in-mecfs-17-may-2016/

 

[Justin30]

A great point was made you ho back to all these original outbreaks of ME and each and everyone of them had Neurological Sequalae ex:

Blurred vission
Muscle twitching
Myclonus
Siezures
OI
Numbness
Tingling
Dysphagia
Headaches
Stabbing pains in the head
Burning
Sleep issues
Pain
GI Dysmotility
Sleep problems

This is how ME was described when the outbreaks started and why it was classified as a Neurological Illness by the WHO.

I just have a hard time understanding that the same illness presents differently if you get these and other types of strange Neurological Symptoms..

That being said I think CFS results in the same outcome.

I personally would like them to look more i into the encephalopathy and the Autonomic Dysfunctioand start experimenting with:

Neuranal Stem Cells
IVIG in Neuro ME
IV Nutrtional Therapies from the get go
Plasmapherises

We have the lowest QOL Scores out of any illness on the planet.

I think its time time to "start the treatment"

I think there is also an AutoImmune subset to this which is in desperate need of better diagnostics and tests that arent just available in the US at the Mayo Clinic.

 

[charles shepherd]

We have now added Dr Karl Morten's excellent powerpoint presentation slides to the MEA website report:

http://www.meassociation.org.uk/201...ondrial-muscle-research-in-mecfs-17-may-2016/

 

[skipskip30]

Why are the MRC still refusing to research actual ME patients, rather than those with Chronic Fatigue?
You could say the answer is obvious, it's the MRC who funded the PACE trial, so that's why.

However, I would like to this Science doesn't always remain twisted.

So please can someone tell me, what's the point at looking at CFS patients who have LOW Cytokine inflammation only and then referring this to a study on ME - when ME is associated to HIGH levels of inflammation?

Is that good quality science? or is it political?

ME means Inflammation of the brain/spinal cord, muscles.

By selecting people with FATIGUE and calling them 'ME' patients, this isn't accurate scientifically or medically.
So why is this still happening? Wrong heterogenous fatigue cohort = no cause of ME ever found.

Who benefits from this? People with Fatigue (yes) or people with Neurological ME (no).

Maybe oneday, someone might like to actually research people with ME (HIGH Inflammation) rather than Chronic Fatigue. If they do,we might get somewhere.

At least Ron Davis over in the USA knows what he's doing, and Dr Montoya who actively research people with ME (ironically then calling it 'CFS').

Your last sentence sums it up for me, I dont think a lot of people (me included) see them as separate things. I dont think we know enough about the illness to start dividing up subsets and when we do I doubt it will be ME and CFS.

 

[Michelle]

@charles shepherd Thanks for the presentation. Unfortunately the sound quality was rather poor so I apologize if I'm simply restating a comment you made but I mis-heard! One of the issues discussed was the lack of funding for ME/CFS research, and Dr. Morten made a comment about the Gates Foundation. A few minutes later there was a discussion about epidemiology of this disease in developing countries (on which, of course, there has been very little work -- like everything else related to this disease) and you mentioned emerging long-term ME-like illnesses from diseases like Ebola. Which made me wonder if that might be a way to tap into Gates Foundation funding. This is a disease that is quite likely having long-term adverse public health consequences in developing countries in the same way as, say, guinea-worm disease.

Granted I can imagine before the Gates Foundation will shell out money for studying this disease, they will want more and better epidemiological data about the impact of this disease on developing countries -- I have no idea if they even fund small and/or pilot studies. And, of course, I have no idea how to take an idea like this and do anything with it. But it was a thought that crossed my mind while watching the presentation -- and may have crossed my mind because you may have been saying the same thing but I couldn't hear properly.

I suppose the clinical trial that the NIH is doing might be a start in the right direction for providing some data, to say nothing of the fact that the PI of said study might be well-suited to connecting such an idea with a grant request to the Gates Foundation given his background in studying Ebola. Certainly from a PR perspective, linking ME/CFS to populations outside the industrialized world would be a good thing. I know I'm often struck by the thought of how much more dreadful ME/CFS would be living somewhere without clean water, or say, civil war.

 

[Hutan]

@Michelle
I've been having the same thoughts, most recently after reading the latest NCNED paper which had patients on their database answer a survey. They essentially concluded that a typical ME/CFS patient was a highly educated female. And they stated that this finding (given the lack of epidemiological studies in Australia prior to this one) could be used to help guide management and thinking about the disease.

But it is obvious that the group of people who sign up to an online database of a specialist institution are not going to constitute an unbiased sample of the ME/CFS population.

Epidemiological work in communities that have never heard of chronic fatigue syndrome could be helpful in so many ways.

Yes, I got excited when I heard about Nath's interest in the post-Ebola syndrome. And yes, those people with post-Ebola syndrome will be among the most vulnerable in the world. They are in countries with under-resourced health systems and little in the way of social welfare systems. They have probably lost many of their family members to Ebola and I understand that the houses and possessions of people infected with Ebola were often burnt. Ebola survivors can carry a stigma that means that, even if able-bodied, they can find it hard to get work and be accepted back in to their communities.

A handful of epidemiological studies showing that ME/CFS is a world-wide problem that is not the result of an infectious meme might help build momentum for biomedical research. How can we progress the idea of epidemiological work in post-Ebola communities or in other disadvantaged communities elsewhere?

I'll contact NCNED and suggest that they do some followup epidemiological work in disadvantaged communities in Australia and/or the Pacific.

 

[charles shepherd]

@Michelle
I've been having the same thoughts, most recently after reading the latest NCNED paper which had patients on their database answer a survey. They essentially concluded that a typical ME/CFS patient was a highly educated female. And they stated that this finding (given the lack of epidemiological studies in Australia prior to this one) could be used to help guide management and thinking about the disease.

But it is obvious that the group of people who sign up to an online database of a specialist institution are not going to constitute an unbiased sample of the ME/CFS population.

Epidemiological work in communities that have never heard of chronic fatigue syndrome could be helpful in so many ways.

Yes, I got excited when I heard about Nath's interest in the post-Ebola syndrome. And yes, those people with post-Ebola syndrome will be among the most vulnerable in the world. They are in countries with under-resourced health systems and little in the way of social welfare systems. They have probably lost many of their family members to Ebola and I understand that the houses and possessions of people infected with Ebola were often burnt. Ebola survivors can carry a stigma that means that, even if able-bodied, they can find it hard to get work and be accepted back in to their communities.

A handful of epidemiological studies showing that ME/CFS is a world-wide problem that is not the result of an infectious meme might help build momentum for biomedical research. How can we progress the idea of epidemiological work in post-Ebola communities or in other disadvantaged communities elsewhere?

I'll contact NCNED and suggest that they do some followup epidemiological work in disadvantaged communities in Australia and/or the Pacific.

Re Ebola virus: From Research (Infection) section of 2016 MEA purple booklet:

Post-Ebolavirus disease syndrome describes a wide range of physical and mental symptoms, including fatigue, joint and muscle pain, headaches, sleep disturbances and short term memory problems, that are now being reported during the convalescent stage in people who have been infected with the Ebola virus in West Africa (Carod-Artal 2015). Prolonged fatigue can also follow a number of other tropical infections, including dengue fever (Seet et al 2007).

 

[Michelle]

@charles shepherd I can't remember the specific study at the moment but I know they've found similar issues post-West Nile virus here in the US of up to 50% of patients. Which for me has always underscored that ME/CFS is unlikely to ever be pathogen-specific but something that occurs as a result of any pathogen, with perhaps the nastier the pathogen, the likelier the chance of developing ME/CFS.

@Hutan I suppose for those of us in the US, we just kinda have to wait on the NIH's clinical study. Though perhaps Lenny Jason's group at DePaul might be a good group to approach about studying underprivileged groups here in the US or elsewhere.

 

[Hutan]

@Michelle - re West Nile Virus

http://forums.phoenixrising.me/index.php?threads/do-mes-cause-cfs.31930/page-34#post-640451


Muscle Nerve. 2014 Jan;49(1):26-9. doi: 10.1002/mus.23869. Epub 2013 Sep 11.
West nile virus infection and myasthenia gravis.
Leis AA1, Szatmary G, Ross MA, Stokic DS.
Author information

Abstract
INTRODUCTION:
Viruses are commonly cited as triggers for autoimmune disease. It is unclear if West Nile virus (WNV) initiates autoimmunity.

METHODS:
We describe 6 cases of myasthenia gravis (MG) that developed several months after WNV infection. All patients had serologically confirmed WNV neuroinvasive disease. None had evidence of MG before WNV.

RESULTS:
All patients had stable neurological deficits when they developed new symptoms of MG 3 to 7 months after WNV infection. However, residual deficits from WNV confounded or delayed MG diagnosis. All patients had elevated acetylcholine receptor (AChR) antibodies, and 1 had thymoma. Treatment varied, but 4 patients required acetylcholinesterase inhibitors, multiple immunosuppressive drugs, and intravenous immune globulin or plasmapheresis for recurrent MG crises.

CONCLUSIONS:
The pathogenic mechanism of MG following WNV remains uncertain. We hypothesize that WNV-triggered autoimmunity breaks immunological self-tolerance to initiate MG, possibly through molecular mimicry between virus antigens and AChR subunits or other autoimmune mechanisms.