Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), 2018, Scheibenbogen et al (EUROMENE)

[Joh]

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y

Background and main text
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies.

Conclusions
Currently available data on the role of chronic viral infection with ME/CFS is still controversial, showing potential viral involvement for at least a subgroup of ME/CFS patients. Therefore, it is necessary to assess the presence and markers of viral activity at the initial stage of the disease to evaluate possible etiological factors and conduct longitudinal studies in order to assess active viral infection and symptom severity variations over time. Moreover, results should be compared not only between ME/CFS patients and controls, but also with other co-morbidities to assess specificity of suggested biomarkers.

Considering ME/CFS heterogeneity, the use of clinical characteristics and biomarkers to enable definition of the disease subtypes is crucial. In addition, longitudinal and standardized studies determining ME/CFS course and therapy effectiveness with follow-up measurements in dynamics should be accomplished. This will allow prognosis of the disease development and promote development of a specific definition for diagnostics and a treatment plan.

Authors:

• Santa Rasa,

• Zaiga Nora-Krukle,

• Nina Henning,

• Eva Eliassen

• Evelina Shikova,

• Thomas Harrer,

• Carmen Scheibenbogen,

• Modra Murovska,

• Bhupesh K. Prusty

• and the European Network on ME/CFS (EUROMENE)

 

[Joh]

Funding
This review is based upon work from European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) as part of COST Action CA15111 supported by the EU Framework Program Horizon 2020 (Website: http://www.cost.eu/COST_Actions/ca/CA15111). Other funding sources—the Bulgarian National Science Fund [ДКOCT 01/9 to E.S.], Solve ME/CFS Initiative, USA (to BKP).

Five Germans from three German universities were involved, but as always not a Cent German research funding.

 

[Joh]

1. Abstract
2. Background
3. Human herpesviruses
4. Enteroviruses
5. Human parvovirus B19
6. Retroviruses
7. Ross River virus
8. Molecular mechanisms behind viral pathogenesis in ME/CFS
9. Conclusions
10. Future strategies for development of infection biomarkers in ME/CFS
11. Declarations
12. References

 

[Inara]

Five Germans from three German universities were involved, but as always not a Cent German research funding.

Yep. But the research has to find answers to ME, says the government. Fuuunny.

 

[Philipp]

This may merit a whole thread of its own, but let's see how far we get here:

Five Germans from three German universities were involved, but as always not a Cent German research funding.

Why is that, actually?

I may be wrong here but as far as I know research grants are not necessarily given out for specific diseases - or at least not exclusively - and I would imagine that there must be some people involved who decide on whether or not to fund a project like this one. I can see rejections based on technicalities in the broadest sense, i.e. no type of grant being available that this type of project falls under so they just cannot fund it or rejections based on 'this is not a test of a hypothesis that will lead to treatment in our opinion', but at this point even a project like PACE was useful in a sense - it told us that CBT is mostly useless (or it would have been in a position to answer that question hadn't the involved people been utterly disingenous/incompetent, but I digress) so it is hard to see why you would not want a thorough writeup on all the common viral triggers that have been discussed over the years.

This leads me to suspect that the people deciding over funding may be biased against research on this topic in general. It is all fine and dandy if research projects are rejected on the grounds that the applications would suggest them not being worth funded, which I cannot realistically judge one way or the other, but as we have seen from the RKI report and other encounters with people involved in policies I do not think it is unreasonable to assume that Scheibenbogen et al may have to deal with people who are simply (to be blunt) pants-on-head retarded.

Does anybody know how much transparency/insight we have on any grant committees that may be involved here, especially regarding CoIs ('hard' stuff like insurance company shills as well as 'soft' stuff like unprofessional anti-science psychobabblers)?
Are there any laws that would make someone liable for flat out ignoring a major health crisis that affects in excess of 100k people in a major way (apart from our GG - while we can always argue with a general notion of human dignity it is almost impossible to translate this into judicial victories, at least from my perception of past issues)?
It is one thing to not have an entire nation do research on a topic because no one has any clue where to look, but it is hard to understand from an outside perspective why establishing a framework like the one from the OP would not be worth allocating at least some resources.

 

[Inara]

Why is that, actually?

I asked the Ministry for Health, but they never replied.
They told me research has to find answers to ME, and that they cannot help. I asked which research projects they or other state institutions funded, and they didn't reply. Still, it's a clear answer.

apart from our GG

Do you mean the Grundgesetz ("constitution")?
The Grundgesetz does not contain - and it cannot be conferred - the right to get health treatment; says the German Bundestag.

The WHO is stricter and grants every human being the right of health (from which follows the right to get treatment). That's another issue in itself, but it's not totally wrong.

 

[Dolphin]

Looks like a review paper. My impression is this is generally not the sort of thing biomedical researchers would apply for grants for from national research entities. You might mention people who are funding your other work.

 

[Inara]

You might mention people who are funding your other work.

I don't understand this?

 

[Dolphin]

You might mention people who are funding your other work.

I don't understand this?

Like Solve ME/CFS Initiative here. I'm pretty sure you won't find that they gave them money to do this paper review. They gave the money to do specific biomedical studies. This is what I have found on a quick search:

Immunometabolism of T cells and monocytes in ME/CFS

A project summary as written by Drs. Scheibenbogen and Sotzny:

Patients with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) suffer from a wide range of physical, neurocognitive and autonomic symptoms. There is a strong evidence for an impairment of the cellular metabolic function and dysregulation of the immune system in ME/CFS. More recently, different research groups uncovered severe metabolic alterations in ME/CFS patients (1-3). There is first evidence that a serum factor causes these metabolic alterations, which might be an autoantibody (3). We could show antibodies against adrenergic (AdR) and acetylcholine receptors (AchR) in a subset of patients with ME/CFS (4). Adrenergic and acetylcholinergic dysregulation may influence cellular metabolism.

The function of immune cells is highly dependent on energy metabolism and synthesis of proteins and lipids. Immunodeficiency or altered immune function is frequently found in ME/CFS. In this project we want to confirm and extend the findings from recent studies of altered metabolites in patients’ serum. The aim of our study is to analyze if the metabolism of T cells and monocytes is impaired in ME/CFS patients and correlates with impaired immune function. Further the suitability of a blood cell-based metabolic assays as potential diagnostic markers will be analyzed. The potential use of metabolic markers in plasma is hampered by the necessity to evaluate a larger number of metabolites for a disease specific profile. In this context we will investigate the relevance of adrenergic and acetylcholinergic stimulation on metabolic alterations as well. Taken together this project will contribute to the understanding of the underlying pathomechanism of ME/CFS and may promote the development of diagnostic markers and potential therapeutic strategies.

AUTOIMMUNE SIGNATURE IN CFS/ME DECEMBER 6, 2016 / VOLKMEDIA / UNCATEGORIZED

A project summary as written by Carmen Scheibenbogen and Madlen Lobel:

There is ample evidence of an autoimmune pathomechanism in a subset of patients with CFS. We could recently show autoantibodies against adrenergic (AdR) and muscarinic acetylcholine (MAchR) receptors in a subset of CFS/ME patients which might be associated with disease pathology (1). Norwegian studies show responsiveness to B cell depletion with rituximab in approximately 60% of CFS patients (2, 3). In this project we therefore want to analyze specific cellular and genetic autoimmune traits in CFS/ME. In patients with and without AdR and MAchR autoantibodies we will analyze the prevalence of single nucleotide polymorphisms (SNPs) with functional impact on genes associated with autoimmune diseases. Further, we will analyze risk variants for autoimmunity in the non-coding genome in form of lncRNAs, as most risk variants with a regulatory function on immune cells are found in non-coding regions. In addition, the frequency and function of immune cell subsets with pathogenic function in autoimmunity including type I IFN producing pDCs and regulatory B cells will be analyzed. Our goal is a better characterization of the subset of patients with an autoimmune cause and to better understand the pathomechanisms underlying autoimmunity in CFS/ME which might result in improved diagnosis and treatment in the future.

Actually, although the Solve ME/CFS Initiative gave money to Carmen Scheibenbogen, in this case reference is specifically made to Dr. Bhupesh Prusty

Team 5: Molecular Mechanism Behind Mitochondrial Dysfunction Indicated, for Further Study

Dr. Bhupesh Prusty, a molecular virologist in the Department of Microbiology at University of Würzburg, designed his 2016 Ramsay project to explore the hypothesis that mitochondrial dysfunction in ME/CFS has a pathogenic connection. He focused on HHV-6 (a herpesvirus that has been implicated in chronic conditions) based on his previous findings of HHV-6 activation and changes to mitochondria.

The preliminary results indicate that HHV-6 activation can lead to changes to mitochondrial structure and function, potentially even in healthy cells via a mechanism of remote activation. Dr. Prusty said “data generated during the project will enable us to write at least 2 manuscripts, which will also create possibilities for us to acquire further grant funding to continue our work.”

Anyway, my general point still stands that I don't think biomedical researchers would generally apply for funding to the national taxpayer-funded medical research entity to write review papers. Generally it seems to me you apply for funding for specific projects where new biomedical data is collected.

 

[Jonathan Edwards]

This is a review written as part of the EU COST Action grant. It includes people from various European countries. This really has nothing to do with funding actual research projects. It is a networking and communications exercise.

As to whether German grant giving bodies give enough attention to ME I suspect not, as for other countries. However, it is always worth remembering that government organisations have been pretty little help for lots of medical conditions. In the UK at least the mainstay of support has tended to be charities. Where there are flourishing charities the original science gets done. Government agencies tend just to fund established lines of enquiry.

 

[JaimeS]

The opening to this paper is a shambles, with a lot of misunderstandings or miscommunications about the basic facts. Maybe it's a translation issue?