MEA RRF to fund study into tests for mitochondrial dysfunction

[mermaid]

The current cost of the test, Kati, is £260 but on top there is a letter of interpretation that goes to the GP (as well as the patient) and that is £110. However it is increasingly difficult for anyone to get the mitochondrial function test done now as Dr Myhill is so busy that she is not taking new patients and even those who have been patients in the past are restricted depending on how recent the contact is, or in some cases just repeat tests only.

I have had the test done twice at a 4 year interval, the first time with Dr Myhill and the 2nd time with another practitioner who works using similar methods. My 2nd test showed a substantial improvement (after using recommended treatments) but I am dubious as I don't really feel I have improved very much if at all. In fact between the first and 2nd tests I had a relapse and don't feel I have ever really got back to the level I was at pre relapse

I do know of a couple of people who had the test done and it showed a better than expected result even though they were more dysfunctional than I am, (ie a much better score than I had on the test the first time) so if the test does have value those aspects would need explanation.

 

[Sasha]

There was a discussion on the commercial test on PR not long ago, including a contribution from Jonathan Edwards:

http://forums.phoenixrising.me/index.php?threads/dr-myhill-publishes-new-book.29377/page-2

Was this the link you wanted?

http://forums.phoenixrising.me/inde...l-publishes-new-book.29377/page-2#post-507375

 

[Sasha]

Post-infectious mitochondrial myopathies are well recognised and this was the initial diagnosis that I received in relation to my post chickenpox encephalitis ME. The MM diagnosis was made by Professor John Morgan Hughes at the National Hospital for Neurological Diseases in Queens Square, London. At the time John was one of the leading experts on muscle disease in the UK and he had seen a number of people with a very similar muscle symptomatology following an acute infection.

Do you think that PWME should be tested for this as standard? Is there a treatment?

 

[charles shepherd]

Do you think that PWME should be tested for this as standard? Is there a treatment?

Simple answer to first Q is NO - the investigation of mitochondrial dysfunction in ME/CFS is still very much a research related activity and would not normally be regarded as a key component of routine clinical assessment in someone with a ? diagnosis of ME/CFS - unless there were symptoms/signs suggestive of a primary muscle/mitochondrial disease

Simple answer is again NO - there is very little in the way of drug treatment available for mitochondrial myopathies at present. And most of it is experimental or very speculative. In conjunction with Professor Peter Behan and the late Professor Mina Behan in Glasgow, we tried a number of 'lateral thinking' interventions using my own skeletal muscle. But without any obvious benefit…….

 

[Gijs]

ME/CFS is not primary a muscle/mitochondrial disease.

 

[Scarecrow]

ME/CFS is not primary a muscle/mitochondrial disease.

I tend to agree with you but all the same there's definitely something up with energy production which is yet to be explained.

to Myhill et al.
to the Netherlands study
to the pilot study data from Newcastle in view of the Netherlands study.

The pilot study is certainly interesting and I'm more than curious to see if it is confirmed. I'm not expecting a cure from this work but it's intriguing and adds to the bigger picture.

 

[charles shepherd]

ME/CFS is not primary a muscle/mitochondrial disease.

I don't think anyone (including myself!) is seriously claiming that ME/CFS is a primary disorder of muscle or skeletal muscle mitochondria

What some of us are saying is that as part of a complex multi system disease process there is skeletal muscle pathology, and mitochondrial dysfunction in at least a sub-group of people who come under the ME/CFS clinical umbrella

 

[voner]

I don't think anyone (including myself!) is seriously claiming that ME/CFS is a primary disorder of muscle or skeletal muscle mitochondria

What some of us are saying is that as part of a complex multi system disease process there is skeletal muscle pathology, and mitochondrial dysfunction in at least a sub-group of people who come under the ME/CFS clinical umbrella

and in that sub group, is it associated with orthostatic intolerance???

 

[charles shepherd]

and in that sub group, is it associated with orthostatic intolerance???

I'm afraid the smile answer is that I do not know - because I am not aware of anyone who has looked at whether orthostatic symptoms and signs are more common or pronounced in people who have evidence of muscle pathology

 

[skipskip30]

I would be fascinated to know what my test results where now as im feeling much worse than when I first had the test 7-8 years ago. Its a large amount of money to spend out on curiosity as the mitochondrial boosting supplements had no effect the first time even though I was estimated to be at around 30% efficiency.

 

[charles shepherd]

I would be fascinated to know what my test results where now as im feeling much worse than when I first had the test 7-8 years ago. Its a large amount of money to spend out on curiosity as the mitochondrial boosting supplements had no effect the first time even though I was estimated to be at around 30% efficiency.

Unfortunately, none of these expensive commercial 'mitochondrial function supplements' have been properly assessed in anything approaching a proper clinical trial and they are not therefore used/prescribed by specialists who deal in primary mitochondrial and muscle disease. Consequently, I do not use or recommend them in relation to ME/CFS.

 

[skipskip30]

Unfortunately, none of these expensive commercial 'mitochondrial function supplements' have been properly assessed in anything approaching a proper clinical trial and they are not therefore used/prescribed by specialists who deal in primary mitochondrial and muscle disease. Consequently, I do not use or recommend them in relation to ME/CFS.

I can fully understand your position. You just get to a point where you will try pretty much anything to feel even slightly better as im sure you understand. Whatever the result this study is a good step forward.

 

[user9876]

Unfortunately, none of these expensive commercial 'mitochondrial function supplements' have been properly assessed in anything approaching a proper clinical trial and they are not therefore used/prescribed by specialists who deal in primary mitochondrial and muscle disease. Consequently, I do not use or recommend them in relation to ME/CFS.

I have a vague memory about someone in the US publishing a trial protocol looking at exercise and supplements for mitrocondria for ME patients. I don't recall any more details and I've never seen any results.

 

[charles shepherd]

I have a vague memory about someone in the US publishing a trial protocol looking at exercise and supplements for mitrocondria for ME patients. I don't recall any more details and I've never seen any results.

This trial is in progress and due to finish in September 2015:

https://clinicaltrials.gov/ct2/show/study/NCT02311257

 

[Sasha]

This trial is in progress and due to finish in September 2015:

https://clinicaltrials.gov/ct2/show/study/NCT02311257

That looks like a survey of what supplements people are choosing to use, not a study of whether they're effective, unless I'm reading it wrong.

 

[charles shepherd]

That looks like a survey of what supplements people are choosing to use, not a study of whether they're effective, unless I'm reading it wrong.

Yes, I would accept that using the term trial here is a bit of a misnomer!

The only clinical trial I'm aware of in relation to ME/CFS and mitochondrial supplements is this one from Columbia but it was withdrawn prior to enrolment

https://clinicaltrials.gov/ct2/show/study/NCT02311257

Others may know what happened here at Columbia…...

 

[charles shepherd]

Comment from Professor Norman Booth on the MEA website:

2 thoughts on “New award from the MEA Ramsay Research Fund for further mitochondrial research | 21 July 2015”

1. 
   HOPEJuly 21, 2015 at 9:09 am
   This sounds very exciting and good news that it has the backing and funding to carry it forward.
   
   Thank you Ramsay Research, MEA and all involved. Newcastle are certainly leading the way in many diseases. It’s good to know the North East has great things to offer.
   
   Thank you
   
   Log in to Reply
2. 
   Norman_BoothJuly 24, 2015 at 3:59 pm
   I am very pleased that finally, another group has decided and been funded to check the Acumen measurements of ATP concentrations in human cells and other aspects of the function or dysfunction of their mitochondria. It is very important to assay mitochondrial dysfunction in a way that is straightforward and which yields the most physiologically relevant, unambiguous and informative results.
   
   In our first paper [1] we showed that 70% of ME/CFS patients had below normal levels of ATP in their neutrophils and all had some degree of mitochondrial dysfunction. In our second paper [2] we found (actually to our own amazement) that for about ½ of both treated and untreated patients, a substantial fraction of their ATP was being produced, not by the electron transfer chain or anaerobic glycolysis, but by another process. We have since then determined that this other process is also anaerobic (no oxygen uptake). In the early days of Dr Sarah Myhill using tests carried out by Dr John McLaren-Howard the functionality of certain enzymes (or complexes) in the mitochondrial electron transfer chain were measured. It was found that the results did not correlate with clinical ability, and over several years the present ATP Profile and other tests were developed. In a recent review of the techniques for assessing mitochondrial function in cells, Brand and Nicholls (reference [11] of our second paper) concluded that the amount of cellular ATP does not necessarily report mitochondrial function because there can be pathways which try to compensate for any dysfunction [3]. In fact, the most likely compensatory pathway (the adenine nucleotide pathway) not only explains the effects that we reported, but also predicts post-exertional malaise, the prime symptom of ME/CFS, on the timescale of a few days [4].
   
   Brand and Nicholls also point out that measuring the functionality of individual mitochondrial respiratory complexes, as planned by Dr Boulton, is not very useful because no single complex is rate limiting [3]. Also, function depends upon the integrity of many processes. The chain as a whole has to function, but it is more like an assembly line – and don’t forget the doors that let the essential parts and co-factors come in, or the door that lets out the final product, ATP.
   
   Many medical doctors use the Acumen ATP Profile and auxiliary tests. It is important that as a first step a second party replicates some of these so that results from the same blood samples can be compared. Where necessary improved techniques can be implemented.
   
   The Acumen measurements take place in vitro but they study blood cells that are still alive. Some of the tests are on mitochondria isolated from the cells, but the mitochondria are still functional.
   
   Ideally, we would like to measure cells in vivo in different parts of the body, for example in skeletal muscle. This is now possible using near infrared spectrometry (NIR) and sophisticated electronics [5] but this technique has not yet been used on ME/CFS patients. It may take some time but I look forward to having an APP on my smart phone to receive and analyze the signals from NIR sensors taped onto my muscles. In the meantime I wish Dr Boulton every success in this new project.
   
   REFERENCES
   1. Myhill, S., N.E. Booth, and J. McLaren-Howard, Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med, 2009. 2(1): p. 1-16.
   2. Booth, N.E., S. Myhill, and J. McLaren-Howard, Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). International Journal of Clinical and Experimental Medicine, 2012. 5(3): p. 208-220.
   3. Brand, M.D. and D.G. Nicholls, Assessing mitochondrial dysfunction in cells. Biochemical Journal, 2011. 435(2): p. 297-312.
   4. Lengert, N. and B. Drossel, In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Biophysical Chemistry, 2015. 202(0): p. 21-31.
   5. Binzoni, T., et al., A new method to measure local oxygen consumption in human skeletal muscle during dynamic exercise using near-infrared spectroscopy. Physiological Measurement, 2010. 31(9): p. 1257-1269.