Researcher Interactions Science for ME Q&A with Dr Montoya, 16th January 2018 question collection thread

Some say the immune system is a little bit like a chaotic system, i.e. if you look at its function at one point in time and then on another, it might be completely different and it might not be forecast in which way. Assuming the immune system is 'chaotic': If the immune system plays a role in ME can a biomarker be found at all?

 

This might be too simple a question (in too many words), please, complier, feel free to skip or critically edit:
What would be your advice to someone who fits the criteria for mild/moderate ME/CFS, is still in the first couple years, but has not identified any significant abnormalities in standard blood tests? Is there a path to a firmer diagnosis through tests or are we not there yet and it's best to simply wait and see what the research brings?
I'm asking from the perspective of someone in a commonwealth country so there are no insurance issues (requiring a diagnosis for funding) and tests are generally not done unless there is a treatment or course of action that might result from it.
How would one pursue a practically useful diagnosis? or at least not miss any important differential diagnoses? Purely from a health perspective and not a financial or political one.
My understanding is that there are a lot of tests that might be useful to research but which are not yet useful to patients (those who don't need to prove anything to insurance). And that there are no treatments as, although some subsets have responded to some things, there are no ways to know which patient subset you are if you're not on a trial.
I realise this looks like a personal question and it is but I suspect there are a lot of people who want to know the answer. If more succinctly stated.

 

Given your focus on the inflammatory nature of ME/CFS, will your research center be pursuing any drug treatment trials? If so, which ones are you considering and why would you consider these treatments as potentially beneficial?

 

In 2013, in a call with the CDC, Dr. Ian Lipkin reported finding retroviruses in 85% of samples sent to him from your lab. We have not heard any follow up over the years. Has this been explored at all? Do you think retroviruses play a role in ME/CFS?

 

Got to admit that I've been wondering if we'd be a bit short of questions for Dr Montoya but compiling them below, and considering we have a planned limit of 30 minutes to our time with him, I'm feeling a lot better about it.

I've done a little bit of editing down, if you feel I've misinterpreted your question then let me know.

Bone Marrow
At the recent CFSAC Meeting you briefly mentioned that there may be a mechanism in the bone marrow? Can you comment on that?

T-cells
Could you elaborate on the findings that you and Mark Davis had with clonal expansion of T-cells and a possible antigen? Can you give us an idea of how big of a discovery you think this will turn out to be if validated and when will we hear more on this and if you think their will be treatments that can target this?

Drug trials
I note that you have done clinical trials in the past on Valgancyclovir (antiviral), and on low dose Methylphenidate (stimulant) with and without Mitochondrial Support.

• Do you still use either of these treatments in your clinical practice?
• Do you have further larger trials of either of these planned?
• Would you recommend either for patients to try?
• Do you have any other drug trials planned?

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Given your focus on the inflammatory nature of ME/CFS, will your research center be pursuing any drug treatment trials? If so, which ones are you considering and why would you consider these treatments as potentially beneficial?

Biomarkers and their implications:
Given that differences between ME patients and healthy controls have been found in the brain, cytokines, the microbiome, metabolites in the blood, and mitochondrial function, can you suggest which seems the most promising source of:

• a biomarker that can be used by all doctors to distinguish ME patients from other fatiguing illnesses
• a biomarker that might lead to a better understanding of the cause of ME
• a useful direction for treatment, such as classes of drugs.

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We have seen a number of small scale studies over the years looking for biomarkers including immune system studies and brain scans. There are a few bigger studies as well. Which of the results do you think may be interesting in terms of potential to show core mechanisms and hence are there any that you feel need larger replication studies.

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Some say the immune system is a little bit like a chaotic system, i.e. if you look at its function at one point in time and then on another, it might be completely different and it might not be forecast in which way. Assuming the immune system is 'chaotic': If the immune system plays a role in ME can a biomarker be found at all?

EDS/MCAS co-morbidity
Given that a large proportion of PWME appear to have the co morbid conditions of either EDS 3 (hypermobile type), or MCAS (Mast cell activation syndrome) or both, can you say if there could be a mechanism for why this is, and do you consider these patients to be a separate sub grouping?

Disease severity and severity level diagnosis
Does he have a view on the likely mechanisms for the relapsing remitting nature of the disease and the likelihood of being able to diagnose severity level via biomarkers/metabolic profiling in the future.

Commonality of disease mechanism
With millions of PWCs experiencing fundamentally the same illness do you believe there’s some common basis in the malaise or in the etiology?

Questions on research
Is me/cfs becoming more of an area of interest for students and researchers?

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What are his research plans? What should be the research priorities?
If he was given $25 million for research tomorrow how would he spend it?
Should there be a medical speciality formally responsible for ME and would this help in expanding research interest?

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Will his research on brain scans be replicated/expanded?

Although Japan and possibly one other group also did brain scans, I believe his work should be expanded and not only include healthy controls but cohorts such as MS, Lyme, ALS, Parkinson, Autism, GWI, EDS, and patients suffering from depression. I include depression patients not because I believe we will have anything in common neurologically with this group but because we have to unwind the damage done by healthcare and psychiatry believing we are mental health patients. I don't believe any group will share our specific neurologic issues and I think that needs to be established.


Impaired PDH and potential subsets
What are your thoughts on the impaired pyruvate dehydrogenase paper by Fluge/Mella?
Do you think there are subsets in ME/CFS, such as those that may or may not respond to Rituximab?

Treatments
Could he take an educated guess on when effective treatments will be found for us....

Food intolerance
Do you think there could be a link between ME/CFS and food intolerances?

About pathogens
You recently said that pathogens have not been excluded as cause of ME/CFS. My question is: what kind of pathogens do you think might be involved, and where in the body do you think the infection is, and what kind of research needs to be done to actually fill this knowledge gap?

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In 2013, in a call with the CDC, Dr. Ian Lipkin reported finding retroviruses in 85% of samples sent to him from your lab. We have not heard any follow up over the years. Has this been explored at all? Do you think retroviruses play a role in ME/CFS?

Useful tests in a clinical setting
What would be your advice to someone who fits the criteria for mild/moderate ME/CFS, is still in the first couple years, but has not identified any significant abnormalities in standard blood tests? Is there a path to a firmer diagnosis through tests or are we not there yet and it's best to simply wait and see what the research brings? How would one pursue a practically useful diagnosis? or at least not miss any important differential diagnoses?

 

@Andy, if you want any translations, please let me know. Thank you for summarizing everything!

 

How to help with sleep problems, day night sleep inversion specifically.

 

Given paediatric issues , could we ask about diagnosis process , PEM and PRS - it would be useful to have perspective from an expert

 

Could you be a bit more specific? Are you interested in what Dr Montoya's diagnosis process is? And, just checking, PRS = Persistent Refusal Syndrome?

 

• Could we ask what his diagnosis process is - as it is a process of exclusion what testing is done and which tests would be "core" given post glandular fever onset with stress prior
• Can he define the differences between CF and CFS in a paediatric setting (it tends to be interchangeable here)
• For diagnosis, treatment and research could he confirm the understanding of PEM - there seem to be some idiosyncracies around this here
• Can he advise re experience of children being severely affected - we now have a situation in UK where PEM will be used as a diagnostic feature of PAWS (pervasive arousal withdrawal syndrome - essentially a means of redefining Perfasive Refusal Syndrome for severe ME in children as a psychiatric illness as it is not accepted that it exists) - could he clarify his understanding of PRS/ PAWS in relation to ME and if he has any experience of same.

@Countrygirl may have other pertinent questions along these lines too

 

Briliant, thank you.

 

You said that Famciclovir was not that effective for certain viruses (sample: hh6v), But use vanciclovir for (hh6v), can you please elaborate on what antivirals are appropriate for the known CFS viruses cases:
EBV
HH6V
CMV
.......

 

This may have been asked already but does he believe that ME/CFS could be an autoimmune disease despite the failure of the rituximab trial.

 

A rather non-technical question, but I would be interested nonetheless. My wife eats a fairly normal diet, so her energy input is also normal; her weight is stable. But, like anyone with ME, she has far less energy usefully available to her. Do you have any thoughts of where the 'wasted' energy goes to?

 

Indeed, the Rituximab trial authors will likely conclude in their scientific publication that Rituximab is not an effective treatment for ME. There are dozens and dozens of targeted therapy (biologics, or monoclonal antibodies, all synonyms) which could be possible treatments, if only we had the target! At this point, we are still looking for biomarkers and for mechanisms of illness. This is all frustrating for us patients wanting to get better.

The Norwegians scientists seemed to have more hope in chemo agent Cyclophosphamide, which is much more toxic and consequential than Rituximab. Their thought was that if may be because Cyclo kills more than B-cells, so the problem we have may not uniquely be in B-cells. As a reminder they do not recommend usage of Cyclophosphamide outside clinical trial. I am looking forward to their upcoming publications.

 

The question you ask pertains to metabolism and basal metabolism, how much energy each one of us require to maintain basic body functions. This may be independant to the pathology that we have.

 

So,is it possible that autoimmunity is still at play? I thought @Jonathan Edwards said at some point that the failure of rituximab in ME patients indicates that it is unlikely to be an autoimmune disease. If it's an inflammatory disorder as some suspect, is that a category of autoimmunity?

 

I would think it is more not a autoimmune of the B cells? Sorry I don't understand immune system much, but ritux failed, cannot still be possible the autoimmune is on the T cells (or NK cells since is where we see isues??)) I don't know but just a question.

 

Autoimmunity is a broad term, meaning that the body’s immune system is attacking its own cells or organs. For instance, type 1 diabetes is an autoimmune disease attacking the endocrine part of the pancreas. Here is wikipedia’s definition of autoimmunity:

By all means continue to read the wiki page, it gets interesting.