Sweden planned study: Cell biological/Immunometabolic changes in myalgic encephalomyelitis, ME, Rosén et al (MECELL)

Professor Anders Rosén and Eirini Apostolou, PhD, at Linköping University are planning a study consisting of 3 subprojects, looking at cytokines, EBV enzyme, antibodies and reactivated retro virus etc in blood and saliva samples from 200 mild, moderate and severe ME patients and 200 controls.
They will be working with the ME clinic Stora Sköndal and Per Julin, Bragée ME Center and Björn Bragée and Bo C Bertilson, as well as Jonas Bergquist at the Uppsala ME Research center.

Due to the pandemic they submitted a change application to additionally test subjects for covid-19, to follow people who get infected, before, during and after the infection, to find clues to what causes the infection to turn into post viral syndrome etc in some patients. For this purpose they added 200 controls (so 400 controls total) and changed the project title to "A study of the immune system's response to SARS-CoV-2 coronavirus to better understand and treat possible fatigue after Covid-19 infection", but the research purpose and everything else in the research protocol is the same.

Both applications have been approved.

Applications to the Swedish Ethical Review Agency (both in Swedish) :

https://www.dropbox.com/s/ejenjpt1pu0361a/Rosén Grundansökan m signatur o bilagor 1 2 3 4 5 12 dec 12 2019.pdf?dl=0

Change application:
https://www.dropbox.com/s/6bnycdlxc6g320w/Rosén Ändringsansökan Dnr 2019-06218 insänt 17 april 2020.pdf?dl=0

 

I didn't know that covid 19 would cause EBV reactivation in so many. This sort of mechanism might explain how different pathogens and triggers can apparently cause a similar illness.

 

Smart move to rapidly extend to post-COVID. Excellent news.

 

I think they're referring to this study? Small though.

https://www.researchsquare.com/article/rs-21580/v1

 

I am not sure it means anything. Antibody levels do not prove reactivation. The other variables tested look irrelevant.

The Swedish study looks to me like re-inventing the wheel. The sad fact may be that if a fashion for biological research in ME starts up it may largely be wasted on repeating searches for things that are not likely to be there and that have shown it isn't there several times before.

 

Thanks for posting this @Anna H !

When you say the application has been approved, does that mean it has received funding and is it ready to start?

If it has received funding, who paid for it? The universities or is there some kind of Swedish research institute where researchers have to apply?

Many thanks in advance!

 

Thank you!

Yes, it's ready to start. The preliminary start date was set to Jan 1st, 2020, but they had to make changes to the original application and then came in with their own change application. I've tried to find out if they have started recruiting but haven't found anything.

In the application it's stated that no financial agreements have been made with any outside parties and that there are no financial interests for anyone involved, I can only assume that means the University of Linköping is financing the study. It's the only information I can find about funding I'm afraid.

Edit: I have sent an email to Anders Rosén, asking if it's correct that the University is funding the studie.

 

@Michiel Tack

I received the following answer from professor Anders Rosén:

"Hi Anna!

Thank you for your email and your encouragement and interest in our research project.

We began the study this spring and have conducted sampling of 103 healthy controls and will begin to include ME patients now in August, as the study aims to monitor immunity once every quarter, including viruses: corona, EBV, HERV.

If you want to join or know of any ME patient who wants to join the study, feel free to contact me or Eirini.

I'm happy to hear that you saw our ethics application and have read up on it.

Regarding the financing - at the moment we don't have any funding from OMF, or RME, but we will apply for grants. Linköping University provides us with premises and instruments, but not with salaries, which are the largest expenses. We have gotten grants from the Cancer Foundation for the overall theme: The connection between Infection-Autoimmunity-Leukemia / Lymphoma, . I have 2 employees and would like to hire another one for the extensive immunological studies we do, but for that we need to apply for additional grants. I myself (as a senior professor) work non-profit with 5% salary. If you know of any more sources of funding, feel free to let me know about these.

Kind regards from the summer cottage in Småland's countryside,

Anders"

I haven't responded yet, thought I would ask if anyone knows of any other potential funding sources before I do?

 

Thanks this is helpful.

ME Research UK might also be an option to apply for funding. https://www.meresearch.org.uk/

 

Yes, thank you!

 

I sent the following letter to Anders Rosén :

[...] Great that you have received a grant from the Cancer Foundation.

Since you are also look at COVID-19 and the development of PVF, the study should be even more interesting to finance, I think, so I really hope that RME and / or OMF can help with funding.

I asked around in the ME community about alternative funding and got the following tips:

https://www.meresearch.org.uk/

Hjärnfonden

Neuroförbundet

The EU perhaps?

(Recently, several parliamentary questions were put to the European Commission regarding the ME / CFS resolution, if it will be followed up on, and whether additional funds will be allocated to investigate the long-term effects of Covid-19 and the link between the virus and ME / CFS, links below.)

https://www.europarl.europa.eu/doceo/document/E-9-2020-003764_EN.html
https://www.europarl.europa.eu/doceo/document/E-9-2020-003909_EN.html
https://www.europarl.europa.eu/doceo/document/E-9-2020-003779_EN.html

I would like to participate but I have hypothyroidism, which was an exclusion criteria, so unfortunately I can't. I also receive home visits from my health care providers at Stora Sköndal because I have severe ME, therefore I wouldn't be able to travel to the clinic once a month for 3 months without getting PEM and risk a deterioration of my condition. Still I'm only at the milder end of severe ME.

This makes me wonder when it says in the study protocol that the research persons will be divided into a mild, medium and severe group, while at the same time it says that blood samples will be collected in conjuction with visits to the ME clinic.

Does this mean that only those who can manage to travel there will be included, or will the patients who already receive home visits from Sköndal and Bragée have blood samples collected during home visits, but it's not made explicit in the protocol?

If this means that all research persons will only have blood samples collected when visiting their ME clinic, I can imagine two scenarios:

Either those with severe ME (which by definition means you're too ill to travel to a health care providera without suffering PEM afterwards and risk a deterioration that can be long-lasting or permanent) will not be included in the study and those who are classified as severe ME actually have moderate ME. This would lead to misleading results that can't be generalized to people with severe ME.

Or, severe ME patients will travel to their clinic 3 times in 3 months and suffer PEM, a worsening of symptoms, which include the risk of permanent deterioration. The tricky thing is that you never know if a deterioration will become permanent or not, so that would pose a great risk to those people, who may not even be aware of it themselves. For me, it took many years to realize this. It is difficult even for many specialists to understand the extent of the risks associated with overexertion.

These are some of my thoughts, I hope it's ok that I share them.

I have talked to several people who are interested in participating and I have conveyed information about the study, etc. to them. Not everyone lives near any of the ME Clinics and they wondered if they could participate from 'a distance'. One person who lives in Gothenburg, for example. I guess it does not work, but wanted to convey that anyway, just so you know there is a lot of interest in your study. [...]


Here is his answer

Thanks Anna!

Your letter was well worth reading, with many good and important advice and thoughts, especially about severe ME-patients.

We will soon begin to coordinate the inclusion of ME patients countrywide in the study and I will make sure to address the issue of home visits then.

Have a great summer!

Warmly,

Anders

 

Havent these markers been looked at many times before without anything coming up?

 

yup

 

Measuring things always raises a chance of finding something but this does not look like efficient use of resources.
I think the project is left over from the work done by Jonas Blomberg, who died a couple of years back I think. Jonas was intelligent and creative but his idea of an autoimmune attack on mitochondrial components was a long shot. Rosén is about my age (70) and formally retired. The two of them published a hypothesis paper a while back.

The other point is that to pick up anything reliably you really need to take the approach the UK ME Biobank have used - getting something close to a population-representative cohort and doing careful control/disease matching. The Biobank team looked at a lot of similar things to those on the Swedish shopping list. They had the advantage of having a world class NK cell group. Whether they found any real immunological signal or not is unclear although the MAIT cell study is interesting.

 

I dont know, I still feel that our best chance of finding something will be when someone has strong PEM. Obviously it would be a challenge ethically and practically, but when it gets so bad i struggle to read, write and exist, there must be something measurable going on, although critically; it might not be traceable in the blood.

Ps: Just to elaborate on why I think it might be easier during PEM, is that I can imagine that years of physiological adaptation to the the disease mechanism, might,make it harder to discover when not in PEM.

Sorry if I went off track a little bit here mods

 

Björn Bragée writes about the study on his Facebook page (5 September):

The study is called MECELL for short. @Anna H, maybe you could add "MECELL" to the thread title and/or as a thread tag, for searchability purposes?

 

Done!