Presentation at EUROMENE - London, UK

[mariovitali]

Here is some info that i would like to share regarding my experience in presenting at the EUROMENE Meeting in London, UK.

First of all, everyone at the London School of Hygiene and Tropical Medicine (LSHTM) gave us a warm welcome. Dr Eliana Lacerda was a really wonderful host making sure that everyone was ok.

The first day (12th September) started with the welcome talks of Professors David Mabey and Allen Foster. At 14:15, Dr Carmen Scheibenbogen started presenting her work and the first surprise for me is when she presented a Network Graph showing EGFR (Epidermal Growth Factor Receptor). I specifically asked her if this was about the same Gene, just to make sure.

Regarding EGFR (which was picked algorithmically and was also mentioned in my presentation), please see here :

https://www.s4me.info/threads/machine-learning-assisted-research-on-me-cfs.5015/page-2#post-97553

Next it was Dr Olli Pollo who discussed more about the role of the ANS to ME/CFS. Norepinephrine and Epinephrine were particularly interesting to me as well as they have also been picked by the algorithms. We had extensive talks with Olli and he described to me his work about LDN.

At night of the 12th we went to a nice restaurant in King's Cross. I took the opportunity to sit next to Carmen to discuss about EGFR and why it appeared on her presentation. Then i started talking about some Genes that i found as candidates and interestingly, Carmen had two of those under her Radar.

Then the 13th of September came which was the day of my presentation. Professor Modra Murovska gave me a full hour to present the hypothesis on how the algorithms have found possible issues to Phagocytosis, Liver Disease, TAM Receptors, ER Stress, Inflammation and Oxidative Stress.

I present some of the slides below :

The figure below depicts the network analysis results, identifying Bile Acid Metabolism issues (CYP7B1, CYP27A1, Oxysterols), Liver Disease, Vitamin K Metabolism and LXR/PPARs :






Then we have Machine Learning, identifying more targets like MFGE8, ABCA1, Liver Disease and the Gut :





Here is a figure that includes many of the topics being picked up algorithmically : Note the inclusion of MFGE8, Oxysterols, LXR, PPARs, ABCA1 and GAS6, PROS and MER that interestingly are Vitamin K-dependent. Note that "Phagocytosis" is mentioned and also "Inflammation" and "Autoimmunity".




I also posted references that EBV, Cytomegalovirus, HHV6, Coxsackie B Virus, Parvovirus B19 and other substances can result in Liver Injury, hypothesizing that it is a Liver Injury that sets the stage for a number of ME/CFS patients. Also note below that a viral infection creates ER Stress (and also interestingly so does Hyperhomocysteinemia as noted below) :




Interestingly TAM Receptor dysregulation can activate T Cells and B Cells and affect NK Cell Repertoire :






More importantly i disclosed that i have in my posession a number of Genes that may be of interest and are readily available for further inspection to ME/CFS Patient cohorts.

I will forward my Research notes to several Researchers of the EUROMENE Network hoping to exchange ideas. I will also email to Dr Charles Shepherd my presentation for his reference. Dr. Luis Nacul and Dr Eliana Lacerda were both at the presentation so they may have the opportunity to discuss further with Dr Charles Shepherd.

I will make anything possible to follow up to exchange findings with LSHTM and other Researchers as quickly as possible. Finally, i also expressed my interest in researching patients having Chronic Hepatitis infections.

Unfortunately it was not possible to upload photos i took, despite their small size.

 

[Amw66]

Well done - it is great that your hard work has had an outlet and may become part of any solution.
Thank you

 

[Alvin]

Here is a figure that includes many of the topics being picked up algorithmically : Note the inclusion of MFGE8, Oxysterols, LXR, PPARs, ABCA1 and GAS6, PROS and MER who interestingly are Vitamin K-dependent.

I am quite familiar with Vitamin K2, it does nothing for this disease in my experience. That said i have not run any clinical trials with lots of patients but its easily available in most countries and non prescription. Frankly it should be in the drinking water instead of fluoride for its bone density, cavity prevention and heart disease protective properties but thats not ME/CFS.

We had extensive talks with
Olli and he described to me his work about LDN.

I am curious about this work if you can give us any details.

At night of the 12th we went to a nice restaurant in King's Cross. I took the opportunity to sit next to Carmen to discuss about EGFR and why it appeared on her presentation. Then i started talking about some Genes that i found as candidates and interestingly, Carmen had two of those under her Radar.

I've seen some of her work and she is going to become a giant in ME/CFS/autoimmunity research.

 

[NelliePledge]

Well done - it is great that your hard work has had an outlet and may become part of any solution.
Thank you

Seconded

And for any non science people like me wondering about ER stress here’s Wikipedia’s article on ER https://en.m.wikipedia.org/wiki/Endoplasmic_reticulum

 

[mariovitali]

@Alvin

We all agree that ME/CFS is a very complex disease. If there was one supplement or a specific combination of supplements working we would have known by now, however some people feel better with specific supplements (e.g Thiamine, Biotin). Unfortunately there are more variables needed to be taken into account since some patients may have Hemochromatosis, Wilson's Disease, Fatty Liver or some other condition that negatively affects Liver function.

Since i cannot post here details, all i can say is that -according to this hypothesis- an optimisation of ER Stress, Oxidative Stress and Inflammatory processes has to take place at an individual level. This is not an easy task and i tried to explain why this is so in my presentation. The best analogy i can give is that if an engine fails in many parts, we have to fix each part with a specific sequence and then start the engine. Any attempt to stress the engine more that it can handle, it will lead again to engine failure hence being back to square one (a vicious cycle)

I hypothesise that Vitamin K can be very important for some patients (note : this is not a suggestion to supplement with it). One researcher said that impaired phagocytosis was found and was very interested to Vitamin K's role in recognising apoptotic cells. Also, PTPN11 was of interest because of its association with T Cells :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3449242/

To summarise, ME/CFS is a candidate for a personalised treatment approach (Hypothesis)

Regarding LDN, i will have to have more discussions but i will let you know as soon as i have more information.

 

[mariovitali]

I forgot to add some important slides.

We may have to see what happens during a Liver injury originating from Viral Infection :



We read that we have alteration of Bile acid secretion, gluconeogenesis, glycolysis, detoxification, metabolism of carbohydrates, proteins fats. I believe we have seen these problems identified before in papers by Naviaux et al, Hanson et al.


Here is a paper from Hanson et.al :




Note also that impaired Bile acid metabolism affects Gut Microbiota. I sent several papers to Derya Unutmaz about this.

 

[Alvin]

We all agree that ME/CFS is a very complex disease.

If ME/CFS is a single disease my personal opinion is that its not as much complex as it is misunderstood. Once we have a disease mechanism we will be able to target it.
Now if its several diseases we will have to identify and name the others.

I hypothesise that Vitamin K can be very important for some patients (note : this is not a suggestion to supplement with it). One researcher said that impaired phagocytosis was found and was very interested to Vitamin K's role in recognising apoptotic cells. Also, PTPN11 was of interest because of its association with T Cells :

Vitamin K2 is an area that should see a great deal more research. And i do think everyone with ME/CFS should be taking it, in fact i think every human should be taking it because its an essential nutrient but was discovered decades later then the ones we all know and has fallen into a scientific purgatory. From brain development to arterial plaque its an essential nutrient that we appear to be designed to be consuming.

Regarding LDN, i will have to have more discussions but i will let you know as soon as i have more information.

I understand, thanks

We read that we have alteration of Bile acid secretion, gluconeogenesis, glycolysis, detoxification, metabolism of carbohydrates, proteins fats. I believe we have seen these problems identified before in papers by Naviaux et al, Hanson et al.

I am reminded of Primary Biliary Cirrhosis which can cause ME like energy deficits because it inhibits pyruvate dehydrogenase function. But its not ME.

 

[mariovitali]

@Alvin

One researcher discussed about PBC and that perhaps I should contact Researchers of PBC. The paper I quoted talks however about consequences of Liver Injury due to HBV. I cannot see the connection with PBC , could you elaborate ?

 

[Alvin]

@Alvin

One researcher discussed about PBC and that perhaps I should contact Researchers of PBC. The paper I quoted talks however about consequences of Liver Injury due to HBV. I cannot see the connection with PBC , could you elaborate ?

Sorry i didn't explain well, i meant that like the Fluge/Mella paper talking about pyruvate dehydrogenase inhibition in ME PBC also causes inhibition in pyruvate dehydrogenase. It may even be worth everyone with ME/CFS being tested for it just in case thats what they have (mine was negative).

I guess at this point there are just theories being put out as to what is ME/CFS, most will turn out to be wrong but from mutated polio to immune deficiency to coxsackie to healing states we are still shooting in the dark and its hard to fully disprove any theory when we don't have a solid one and only a bunch of clues and observations and inferences.

 

[mariovitali]

I present below the questionnaire i compiled for the presentation (although it was not shown) . The questionnaire had 80 responses, here are the results :


We start with infections : EBV is by far the most frequent, Lyme had more answers in the "Other" option





Next we have about specific conditions (DILI = Drug-induced Liver Injury) :




Finally i asked about specific surgical procedures :





The responses shown having frequency of 1.3% are mainly Appendix removals.


We know that Web Questionnaires have inherent problems and so we cannot draw any conclusions with high confidence and this was the reason for not showing these results to the presentation. However i would like to ask whether we have any large scale study showing the prevalence of elevated Liver enzymes vs Controls. Also the "Bowel Resection" frequency in ME/CFS patients could be of interest.

 

[Inara]

Then i started talking about some Genes that i found as candidates and interestingly, Carmen had two of those under her Radar.

Which genes are these?

More importantly i disclosed that i have in my posession a number of Genes that may be of interes

Which ones?

How do you create these networks?

 

[Inara]

Vitamin K2 is an area that should see a great deal more research. And i do think everyone with ME/CFS should be taking it,

I take Vitamin K complex, but my feeling is it does nothing with my symptoms. Maybe the dosage is too small. But I don't think it's a game changer, though I agree it's an important nutrient.

 

[Alvin]

I take Vitamin K complex, but my feeling is it does nothing with my symptoms. Maybe the dosage is too small. But I don't think it's a game changer, though I agree it's an important nutrient.

Do you take K1 or K2?
If K2 MK4 or MK7 or both?
I followed K2 research a few years back for likely unrelated reasons, like ME/CFS its vitally important but very understudied.

 

[Inara]

Do you take K1 or K2?
If K2 MK4 or MK7 of both?
I followed K2 research a few years back for likely unrelated reasons, like ME/CFS its vitally important but very understudied.

All of those you mention in a high dosage, therefore I only take one capsule per week.

I'm interested to know more.

 

[Alvin]

All of those you mention in a high dosage, therefore I only take one capsule per week.

I'm interested to know more.

Well K1 is found in vegetables, is involved in blood clotting and a few other things
K2 is in many forms but two are the most studied
MK7 is made from fermented soybeans and is cheap to produce and will perform some of the functions MK4 does.
MK4 is found in animals which convert it from K1 that they eat. But this works for pasture raised/free range animals. Factory farmed animals are raised on grains and corn so have very little K2 in their bodies.

K2 has many functions, some which MK7 can do but MK4 does all of them. From activating osteocalcin (which has other pathways but those diminish as we get older) to forming matrix gla protein which prevents hardening of the arteries to several immune functions that are not yet well researched to formation of things in the brain. Humans cannot produce it (though some believe we can but it is found in breast milk, interestingly in that case produced in the body). When consumed the body stores most of it in the brain, pancreas, liver and a few other places.
Its research is only early stages but several of its functions have not yet been elucidated while some require K2 otherwise they don't happen.

MK7 has a half live of several days, MK4 a few hours, but unlike MK7 MK4 is stored by the body.
Required doses have not been conclusively worked out but some research suggests the body prioritizes it so low levels would only allow certain functions, but it has been found that 360mcg/day MK7 or 900mcg/day MK4 will fully activate osteocalcin, but the other 16(?) functions no one knows.

 

[mariovitali]

@Inara @Alvin

As i am new to this, i do not know if i can disclose these Genes at present.

Unfortunately it is not about K2 only. I believe that Dr Davis at one point mentioned something about personalised regimen and according to this hypothesis this is what is needed. I cannot say much now but the fact that some people take supplements (e.g Thiamine) , they feel much better and after some time they are back to square one does have an explanation.

A good example would be to imagine a bucket with -say- 10 holes in the bottom of the bucket. If you pour water into the bucket and you block 6 of them, the bucket will eventually emtpy because 4 holes are still open and the water goes away. You have to block all of them. Blocking combinations of 8 holes will eventually empty the bucket because at any one point 2 holes are not blocked and the water will flow through them.

 

[Alvin]

I believe that Dr Davis at one point mentioned something about personalised regimen and according to this hypothesis this is what is needed. Unfortunately i cannot say much now but the fact that some people take supplements (e.g Thiamine) , they feel much better and after some time they are back to square one does have an explanation.

Not only is the placebo effect a thing people can over extend themselves in our disease and pay for it later. Also if our disease is controlled by some mechanism which is likely then pushing on something is likely to cause either a reaction or compensatory mechanism even if its delayed.

In the end we have very little understanding of this disease and a million theories on what it is. As i mentioned earlier from mutated polio to sensitization (sic) to hysteria (facepalm) to nutrient deficiencies and EM fields (i kid you not) everybody has their own theory and almost all if not all are wrong.

 

[Inara]

As i am new to this, i do not know if i can disclose these Genes at present.

Were these genes mentioned in the presentations? As the conference was public and there will be a DVD with the talks (if I remember correctly?), this information could be shared.
If it was only a private conversation, that's something else.

 

[mariovitali]

Were these genes mentioned in the presentations? As the conference was public and there will be a DVD with the talks (if I remember correctly?), this information could be shared.
If it was only a private conversation, that's something else.

These were mentioned on a private conversation. The conference was not public as members of the EUROMENE Network were only present. To the best of my knowledge the presentations were not recorded.

 

[Inara]

Oh sorry, I was mixing things up