Fundraiser: A Novel Proposal for the Treatment of ME/CFS

[AndyPR]

For my PhD research work I am interested in investigating the chronic condition Myalgic Encephalomyelitis (ME), sometimes referred to as Chronic Fatigue Syndrome (CFS). ME/CFS is a debilitating condition affecting approximately 250,000 people in the UK, and roughly 1,000,000 people in the USA. Symptoms include extreme levels of fatigue, post-exertional malaise, muscle pain, cognitive dysfunction, autonomic dysfunction, postural orthostatic tachycardia syndrome, gland swelling, and hypersensitivity to pain and general stimuli (i.e. light and sound). The condition is thought to be triggered by a pathogenic infection, predominantly viral, however no single pathogen is responsible.

I intend to assess my own novel treatment idea for viability in my PhD studies. I currently have a manuscript under peer review for publication in the journal Fatigue: Biomedicine, Health & Behaviour. My article puts forward novel pathophysiological hypotheses, with evidence from a review of the established biomedical literature linked to the symptoms experienced by patients, and explains my novel biomedical treatment idea. I will be sure to link the article here if it is published. The research proposal has received favourable feedback from Dr P. Manning, and a second leading ME/CFS researcher. They have offered to supervise the project from a biomedical and clinical perspective respectively, pending the acquisition of appropriate funds. The only factor delaying the commencement of my work is funding.

http://www.crowdfunder.co.uk/a-novel-proposal-for-the-treatment-of-mecfs

Personally I'd need more details before I'd put any money in but it's a least one example of researchers not being put of from ME research.

Tagging @Hip as Myhill studies are referenced on the Crowdfunder page.

 

[AndyPR]

Also saw this as it was shared on the MEA's Facebook page. Hopefully now we'll see the MEA regularly sharing details of all studies that need funding??

 

[ukxmrv]

I've lost the link to his Facebook page but last night I saw a new post there explaining his hypothesis in a little more detail. It's about ATP but my brain problems stopped me from reading it properly.

 

[charles shepherd]

A CROWD FUNDER FOR GARETH ETTERIDGE'S RESEARCH PROJECT

Helen Hyland, MEA fund-raising manager, writes:

Gareth is a keen and long standing supporter of The ME Association. We sincerely hope that his 'novel' research secures all the funding it needs to proceed.

http://www.crowdfunder.co.uk/a-novel-proposal-for-the-treat…

Gareth was one of the students that we funded to attend the 2016 CMRC conference in Newcastle

 

[AndyPR]

I've lost the link to his Facebook page but last night I saw a new post there explaining his hypothesis in a little more detail. It's about ATP but my brain problems stopped me from reading it properly.

Details are on his Crowdfunder page, both for his Facebook, Twitter and blog, and his slightly-expanded theory, which in a nutshell is that "This project aims to give rise to a method by which ATP can be provided to body cells, with the view of acting to ease patient suffering.".

Personally I'm not convinced by that at the moment as Fluge and Mella are pointing out a problem converting glucose before the ATP stage - I don't believe more ATP will fix this issue, if Fluge and Mella are correct.

 

[charles shepherd]

I don't think Gareth is a member of the PR forum

So if anyone wants to ask him a question he is dealing with questions at the moment on the MEA Facebook page:

https://www.facebook.com/ME-Association-171411469583186/

 

[Hajnalka]

From the crowdfunder page:

My name is Gareth Ettridge, I am currently a student studying for a Master’s Degree in Genetic Manipulation and Molecular Cell Biology at The University of Sussex. I also hold a First Class Honours Bachelor’s Degree from The University of Surrey in Chemistry. I am now looking to raise funds to enable me to study at PhD level.

 

[Hajnalka]

Just started watching his crowdfunder video. His girlfriend Chloe has ME and he is determined to help her. Romantic!

 

[Hip]

Personally I'd need more details before I'd put any money

Looks like an interesting concept: rather than fixing the energy metabolism dysfunction in ME/CFS to that patients can produce sufficient ATP energy in their cells, this PhD research appears to be about trying to supply ATP energy to the cells by alternative means, to help make up for the shortfall.

It says this at the bottom of the proposal:

I propose that one of the main symptom causing factors in ME/CFS is a deficiency in the energy currency molecule: adenosine triphosphate (ATP) [1-3]. Just one effect of an inability to effectively produce ATP is the indirect exposure of muscles to unwanted acid, as a result of anaerobic (non-oxygen using) processes. This project aims to give rise to a method by which ATP can be provided to body cells, with the view of acting to ease patient suffering. This could be viewed as being analogous to putting refined petrol (ATP) in a car petrol tank, rather than crude oil (food, e.g. sugars), or changing the car oil/battery (supplements e.g. vitamins).

It is worthy of note that a deficiency of ATP would affect all cells, from muscles to the immune system.

Note that this PhD research I don't think will be about just supplying ATP as a supplement (you can buy ATP as a supplement anyway), because the average human body gets through around 100 kilograms of ATP each day to meet its energy needs (more than your own body weight in ATP).

This is why the energy metabolism constantly recycles spent ATP, so in fact the same ATP molecules are used to supply energy over and over again. But if it were not for this recycling, you would need to consume 100 kilograms of ATP each day, which is obviously completely impossible.

So I imagine that this PhD proposal will be more about a treatment that helps recycle the ATP in order to provide energy.

 

[AndyPR]

@Hip So has it been shown that we are deficient in ATP then? My, admittedly very limited understanding, of the recent Fluge and Mella results indicate a constriction of the processing of glucose into the mitochondria but, from memory, didn't have anything to say about quantity of ATP itself. My interpretation was that there is a shortage of fuel, converted glucose, not necessarily a shortage of fuel transporters, ATP.

 

[Hip]

@Hip So has it been shown that we are deficient in ATP then? My, admittedly very limited understanding, of the recent Fluge and Mella results indicate a constriction of the processing of glucose into the mitochondria but, from memory, didn't have anything to say about quantity of ATP itself. My interpretation was that there is a shortage of fuel, converted glucose, not necessarily a shortage of fuel transporters, ATP.

The Myhill, Booth and McLaren-Howard studies certainly measured and demonstrated a shortage of ATP in the cells of ME/CFS patients — and also discovered why not enough ATP is being produced in ME/CFS: they showed this is likely due to blockages in ATP recycling in the mitochondria (oxidative phosphorylation), and blockages in the translocator protein (translocator protein transports ATP made in the mitochondria into the cell).

Myhill et al use the term "translocator protein" to refer to the adenine nucleotide translocator (ANT).

The recent Fluge and Mella metabolomic study did not directly measure ATP levels in the cell, but as you point out, found a blockage in the processing of glucose into the mitochondria, which would most likely lead to a shortage of ATP.

 

[Murph]

FWIW Naviaux found women had ATP levels at 97% of controls, according to my analysis of his metabolite data. For some reason the molecule was not measured in men.

I respect Mr Ettridge's genius and his motivation, and I've donated. Nevertheless, from what I know of science PhDs you're lucky if your experiments hold up well enough to learn anything about your hypothesis, and to get a paper or two accepted about your methods. Inventing novel treatments in your first independent project is probably not unheard of but not exactly common.

 

[Hip]

Naviaux found women had ATP levels at 97% of controls, according to my analysis of his metabolite data.

Can you point out where in Naviaux's study you got that from please.

 

[alex3619]

the average human body gets through around 100 kilograms of ATP each day to meet its energy needs (more than your own body weight in ATP).

Yes. ATP is created and destroyed and recreated so fast that the total number of molecules in a day is staggering. You can alter the AMP and ADP pools, but you still need to be able to create ATP. Supplementing ATP is useless from an energy perspective, but might be useful as an extracellular trigger if that is what you want to do. Increasing the total pool that is being turned over may have some impact though, its hard to assess until somebody finds out what effect that has in ME patients.

 

[alex3619]

Using ATP levels as a direct measure of energy available has problems, its more about how much is being utilized over a given time frame than the total quantity. If you have less ATP synthesis but use much less then ATP levels might even be high. Yet you still wont have energy.

 

[Murph]

Can you point out where in Naviaux's study you got that from please.

The paper itself included the key metabolites, but the data made public here had all of them:

http://www.metabolomicsworkbench.org//data/DRCCMetadata.php?Mode=Study&StudyID=ST000450

I've done my own simple analyses of several of them and shared them in a few threads here.

Here's a chart of the raw data for ATP levels in female patients and controls. I've not tested for statistical signifcance, but the ratio of the means is .97. Just by eye-balling you can see there's only a minor difference.



@Hip If you've not seen it in the other thread I put it in you might be interested in this analysis of amino acids I took from the same dataset. Like Fluge and Mella it shows that sufferers have higher concentrations of Group I aminos than of group II. Unlike Fluge and Mella it shows Group I aminos higher in sufferers than controls, while group II are roughly equal in sufferers and controls.

 

[Hip]

@Murph
Did Naviaux et al measure the ATP levels from cells directly taken from ME/CFS patients, as opposed to cells taken from ME/CFS patients and then grown in culture, because the latter method is known to produce errors (see this post).


If you look at Figure 2A from the Myhill, Booth and McLaren-Howard 2009 study, they found healthy controls had on average ATP levels around 2 fmol per cell, whereas ME/CFS patients had on average around 1.2 fmol per cell, with some patients having as little as 0.9 fmol per cell.

So as a percentage, ME/CFS patients on average have only around 60% of the ATP of healthy controls, according to the measurements made in the Myhill, Booth and McLaren-Howard studies.

 

[Murph]

@Murph
Did Naviaux et al measure the ATP levels from cells directly taken from ME/CFS patients, as opposed to cells taken from ME/CFS patients and then grown in culture, because the latter method is known to produce errors (see this post).

I *think* all the Naviaux data is based on plasma levels of metabolites. is that right? What that might infer about the levels of various metabolites we'd expect as compared to in the cytosol or within mitochondria is way beyond my pay-grade.

 

[AndyPR]

Posted on the fundraising Facebook page

After much deliberation and consideration, I have decided to cease crowdfunding activity for the project for the time being. All backers have had their pledges cancelled and no money will be debited. This decision has been taken due to a combination of factors:

It is clear that the target amount will not be reached in the allowed timescale. Furthermore, the peer-review time for my ME article is far greater than expected, and it is not fair to continue to put calls out for donations without peer-reviewed evidence; this also limits my ability to publicise the project beyond those who have preliminary knowledge of ME (let alone of its existence). Once this review process is completed I will return to fund raising if it is required.

I would like to thank everyone who has supported this project, either financially or through raising awareness of it.

The ME patient community truly is inspirational and I assure every one of you this is not me giving up on my ideas, it's going to take a lot more than this to put me off of ME research. However, I am recognising the current situation and I believe I am taking the necessary and appropriate actions.

I will also be shutting down all social media pages for the project: Twitter, YouTube and the WordPress blog, I will leave this Facebook page online for a few days to ensure everyone sees this particular post.

Once again, thank you for your show of support for this project. Now is just not the right time, but I will do everything I can to join the biomedical ME research effort as soon as I can, this isn't the last you've heard of me yet.