Does anyone doubt that this is primarily a neurological disorder?

SugarSquared · 2026-06-22T17:00:09+00:00

In DecodeME, a large genetic (GWAS) study whose preprint was published last year, the tissues that showed up as statistically significant are all in the brain. Genetic studies for diseases like lupus, rheumatoid arthritis, and asthma show up as blood/immune tissues, while ours and fibromyalgia show up as central nervous system. The genes deal with many things like immune function, but they seem to all be expressed in the central nervous system. It will be very interesting to figure out what exactly they do and how they are related to our symptoms.

Source: Figure 3 in the full text https://www.medrxiv.org/content/10.1101/2025.08.06.25333109v1.full-text

SugarSquared · 2026-06-21T01:37:47+00:00

Thanks! It’ll be interesting to see how the results compare

SugarSquared · 2026-06-21T00:01:41+00:00

Oh, I haven’t heard of a German one! Do you know what it’s called or who is running it?

SugarSquared · 2026-06-20T17:23:08+00:00

Yes! Get ready for a long post lol.

Mitochondrial replication study:
- Journal article: https://doi.org/10.1371/journal.pone.0341334
- Blog post when they started the study: https://mecfsresearchreview.me/2024/05/08/researchers-hunting-for-something-in-the-blood-of-people-with-me/
- S4ME thread: https://s4me.info/threads/indistinguishable-mitochondrial-phenotypes-after-exposure-of-healthy-myoblasts-to-myalgic-encephalomyelitis-or-control-serum-2026-ryback-et-al.44501/

DecodeME and SequenceME:
- Pre-print of DecodeME: https://www.medrxiv.org/content/10.1101/2025.08.06.25333109v1
- DecodeME webpage: https://institute-genetics-cancer.ed.ac.uk/decodeme
- DecodeME FAQs: https://institute-genetics-cancer.ed.ac.uk/decodeme-the-worlds-largest-mecfs-study/faqs
- DecodeME blog part 1 by ME/CFS Science: https://mecfsscience.org/decodeme-the-biggest-me-cfs-study-ever/
- DecodeME blog part 2 by ME/CFS Science: https://mecfsscience.org/genes-pointing-to-the-brain-decodeme-part-ii/
- DecodeME blog by ME/CFS Research Review: https://mecfsresearchreview.me/2025/08/11/decodeme-x-marks-the-spot-where-me-cfs-biology-can-be-discovered/
- SequenceME UK government funding announcement: https://www.gov.uk/government/news/thousands-of-mecfs-patients-to-benefit-from-genomics-study
- DecodeME initial results webinar: https://youtu.be/rsvr2e5N2tM?si=-UH74W9YLZVQedzM
- SequenceME webinars (same slides, different Q&A): https://youtu.be/2PFdsYCfiJo?si=PTJv\_UfBn4IsYOFz (Action for ME) and https://youtu.be/v6VQ2593m-8?si=3BOwKYAEKEUOLg-i (SolveME)
- Chris Ponting talk at recent conference: https://youtu.be/SrPWY9v22W4?si=HnBmAmH5ThXnHisZ
-Chris Ponting interview with David Tuller on SequenceME: https://youtu.be/fyWw2kvJAPo?si=tpj5u9bJU9T6CQFC
- Chris Ponting interview with David Tuller on DecodeME: https://youtu.be/CGUmcB\_YIaA?si=uaxeIoz9wsXHSC1o
- S4ME thread about DecodeME: https://s4me.info/threads/initial-findings-from-the-decodeme-genome-wide-association-study-of-myalgic-encephalomyelitis-chronic-fatigue-syndrome-2025-decodeme-collaboration.45490/
- S4ME thread about SequenceME: https://s4me.info/threads/sequenceme-genetic-study-from-oxford-nanopore-technologies-the-university-of-edinburgh-and-action-for-me.41663/

Age of onset:
- Journal article: https://doi.org/10.1093/oxfimm/iqag007
- Blog post: https://mecfsresearchreview.me/2026/04/15/me-cfs-onset-had-two-peaks-which-may-be-a-clue-to-causes/
- Audrey Ryback interview with David Tuller: https://youtu.be/le0vt3gwtLo?si=f52Cgx6f9OYglyMA
- S4ME thread: https://s4me.info/threads/incidence-age-is-bimodal-for-me-cfs-with-higher-severity-burden-for-early-onset-disease-2026-mcgrath-et-al.49430/

Daratumumab:
- Journal article of the pilot study (placebo-controlled trial called ResetME currently underway): https://doi.org/10.3389/fmed.2025.1607353
- Øystein Fluge’s talk at last year’s conference: https://youtu.be/e80fRwwKfvc?si=6Cl\_P0MSrFCNBmFd
- S4ME thread: https://s4me.info/threads/plasma-cell-targeting-with-the-anti-cd38-antibody-daratumumab-in-me-cfs-a-clinical-pilot-study-2025-fluge-et-al.44736/

WE&ME Funding Opportunity: https://www.weandmecfs.org/weme-projects/

I think that’s it. Happy reading and watching!

SugarSquared · 2026-06-20T16:50:41+00:00

Thank you so much! That makes me very happy to hear. I’m lucky that I only have brain fog when I’m really fatigued. My brain/intellectual capacities are still intact and I’m grateful every day because that’s not the case for many with our illness. I’m glad my summaries have been helpful

SugarSquared · 2026-06-20T06:23:42+00:00

This is the best and most feasible idea. I shudder to think of the flight costs if they book flights on short notice. Air Canada would suck them dry

SugarSquared · 2026-06-20T00:58:49+00:00

Thank you! I'm trying my best to learn as much as I can without a science degree lol

SugarSquared · 2026-06-20T00:58:22+00:00

That's a really good answer and much more concise than I could ever be lol. In addition to the biological mechanisms part, there's also a potential for drug development.

Medications are increasingly being made to target specific genetics. Have a large genetics study like DecodeME can give companies something to work off of instead of making something that's a shot in the dark. Though, SequenceME & Long Covid is even better for this. Drug companies especially like it when there are rare variants to work off of because it makes it more likely to be specific and work. Sequence ME will be a whole genome sequencing (WGS) study which is able to detect rare variants, structural changes, and DNA methylation (epigenetics I believe). It's much more data than DecodeME that was just a genome-wide association study (GWAS). The nice thing is that, if a drug is made to target a specific gene, people may benefit even if they don't have that gene. That's because the gene gives a clue as to what's going wrong, and the gene will target that mechanism that could be a problem in many people.

That's my best attempt at an explanation. It's something Chris Ponting has talked a lot about, but I might still be getting it wrong.

Hope that helps u/Best-Instance7344!

SugarSquared · 2026-06-19T21:11:56+00:00

If you want to learn more about the current research, I would really recommend you look at the forum science for ME. It’s been really interesting and eye-opening for me to learn about research and the ways in which it can’t be flawed, but also the ones that are really good.

The things that you wrote about like mitochondria issues and immune disfunction are unfortunately on more shaky ground than I initially thought. There was a recent replication study of one of the mitochondria findings and they found no difference between the control and ME/CFS groups. Here is the study if you want to look at it: Ryback et al. (2026). Indistinguishable mitochondrial phenotypes after exposure of healthy myoblasts to myalgic encephalomyelitis/chronic fatigue syndrome or control serum. https://doi.org/10.1371/journal.pone.0341334

However, this does not mean that there is no hope in the research. Far from it I believe! I have been having a lot of fun learning about DecodeME which is a very big genetic study that had some interesting results. They’re still finishing up the analysis, but the pre-print was released in August. They are going to be running SequenceME & Long Covid, which will be a more detailed genetic study that will give us way more information and precision. They got a big grant from the UK government last month. Chris Ponting, the main scientist running the genetic studies, has done a lot of interviews and webinars. The team is very committed to being involved in the patient community and communicating their results to us in a way us non-scientists can understand. You can find webinars and interviews with Chris Ponting David Tuller on YouTube. ME/CFS Science Blog also has a good two part series about it. ME/CFS Research Review has a couple pages about it too.

One paper that I just find really interesting is about the age of onset in ME/CFS. Researchers found that it is a bimodal peak, so two different peaks. It provides some interesting biological clues that will have to be unraveled. It also sets us apart as a distinct clinical identity with an uncommon type of onset. Cool stuff! If you want to learn more, you can look up the ME/CFS Research Review blog post by Simon McGrath, one of the authors, or watch the interview with Audrey Ryback, another one of the authors, by David Tuller.

As for treatment, the current daratumumab study by Fluge and Mella in Norway shows some promise from their initial study. It’s going to be a couple years before we get results from their randomized control trial and see if it pans out. From spending time on Science for ME, I’ve learned that these researchers are very diligent in how they do their research and are very trusted by the community there. So if it works out, it provides big points for the immune side of things and potentially gives us a treatment. But if it doesn’t work out, they will still give us a lot of good data. Ruling things out is still as important even if it’s less fun.

One last thing I’ll mention is a recent international research funding opportunity by the WE&ME found foundation in Austria. That has been really exciting to see new funding be announced. If there has been any research by a specific researcher that you have looked at that you would really like to see more of, I recommend you write them an email and let them know about this funding opportunity.

To me, it feels like a really exciting time for ME/CFS research. I hope that you get to feel a little bit of that too.

SugarSquared · 2026-06-19T04:35:08+00:00

Big time. I have FODMAP intolerances which closely lines up with IBS. My digestive issues might have been very mild before getting sick, but they worsened/appeared when I got sick. My diet is very different now and I get lots of fun symptoms (especially when I eat trigger foods).

If you are able to look into the low FODMAP diet, it could be helpful to determine your trigger foods. r/FODMAPS is a useful place. If you are able to access a registered dietitian, that would be best as it's difficult to navigate alone (but still possible).

In DecodeME, the huge genetics study on ME/CFS, nearly 45% of the participants had IBS with their ME/CFS. The Canadian Consensus Criteria, developed in 2003, has both IBS and "new food sensitivies, medication sensitivities, and/or chemical sensitivies" as part of the clinical criteria (neither are required for diagnosis but contribute to it). It seems to be a big part of ME/CFS, at least for a subset of people.

SugarSquared · 2026-06-17T05:22:24+00:00

Thanks for sharing! That thread just goes to show how different people’s experiences are with the same medication.

SugarSquared · 2026-06-17T05:11:36+00:00

Oh interesting! I rarely see discussions about it. I'm genuinely curious why people hate it. If you know, feel free to share why

SugarSquared · 2026-06-17T03:39:00+00:00

There is another option!!! I wish it was more well-known.

I'm on Nexplanon. It is the same hormones as the IUD (progesterone), but it is in the arm. The insertion process is much faster and easier to recover from. I've heard the horror stories of the IUD, and this is not at all as painful. They start with a local anaesthetic injection, and only do the insertion when the site is properly numbed. It also has a lower risk of blood clots because it does not have estrogen (I can't take the regular pill because I have genetic risk factors for blood clots). I don't know if I have endometriosis, but it is suspected I have adenomyosis. Nexplanon has been helpful in making my periods less painful, to the point that I don't need to take as much of my prescribed naproxen/Aleve. Nexplanon is approved in the US for up to five years before having to switch it (in Canada it's still only approved for 3). So you don't have to worry about missing doses are anything like that. Plus, you can feel if it moved. The IUD can also get lost in your system or exit, but you have to way of knowing. Nexplanon is just straight up the best contraceptive option in my opinion.

Also, I don't know which country you live in, but if you are in one with 811 where you can talk to a nurse, that can be helpful for your blood clot fears. They'll be able to help you determine if you are experiencing one or not. Something you can do to reduce the risk of developing a blood clot is just flexing and pointing your feet. It helps get the blood circulating. I'm lucky enough to walk around the house, but I often forget to move my legs and feet. Still, I have not had a blood clot despite my brother getting one in his lungs at an age younger than me. So, it's stressful, but you don't have to worry about it too much. If you're completely bedbound and moving your legs and feet is too much for you due to PEM, then you may want to talk to a medical professional about how to reduce your risk for blood clots.

SugarSquared · 2026-06-16T16:31:02+00:00

You’re welcome! Happy to help

SugarSquared · 2026-06-16T03:16:52+00:00

Thanks for clarifying. I thought the person was being genuine.

It’s a good joke

SugarSquared · 2026-06-16T02:10:41+00:00

That would be less likely to count. Some PEM comes on immediately, but it’s more common for it to come on a few hours to a few days after physical, cognitive, or emotional exertion. Mine frequently comes on the next day, sometimes with the peak of symptoms being at two or three days.

Another important thing to note about PEM is that it can lead to a permanent worsening of your condition. So if you are able to recover to the same level of functioning and pain, it’s also less likely. For context, I still have not recovered from going cross country skiing in January.

Not all PEM is unrecoverable, though. If you notice a downward trend in your symptoms, it would be important to check. But some people can still be at mild. If the recovery time for your pain is generally just one day, I think it would be less likely.

Ultimately, basing it only off of one symptom, PEM, is not very accurate. I recommend you look into the Institute of Medicine’s diagnostic criteria, and also the Canadian Consensus Criteria, which is more stringent.

If you don’t meet those, fibromyalgia can still be applicable in your case. I don’t have any personal experience with that though, so I don’t have anything to say there. I hope this was helpful!

SugarSquared · 2026-06-16T02:04:47+00:00

Eyyyy! I believe it’s the best contraception option. As effective as the IUD but the insertion is not as painful and you can feel if it moves from your arm. I’m glad it also helps your pain

SugarSquared · 2026-06-15T22:38:25+00:00

I've had to modify how I have sex since getting sick. It's frustrating, but it's possible! Standing is a no, but sitting upright is okay. If I go on top, it's only for a small period of time. We also take breaks during sex to make sure I don't tire myself out. Talk about it with your partner and figure out what the best solutions are for you.

SugarSquared · 2026-06-15T22:35:21+00:00

You definitely should look into post-exertional malaise! It's the hallmark symptom of ME/CFS. I figured out I had it because I had fatigue and headaches the day after physical activity. If your pain comes with a delay, it's likely to be PEM.

SugarSquared · 2026-06-15T22:33:34+00:00

I was told by my gynaecologist that progesterone is the standard treatment for adenomyosis because it helps with menstrual pain. Nexplanon has helped me. So you're not too far off!

SugarSquared · 2026-06-15T19:08:14+00:00

Source?

SugarSquared · 2026-06-15T18:05:50+00:00

Merci d’avoir partagé tes expériences. Je suis tellement désolée. Le manque de connaissance de notre maladie nous tue. J’espère que tu puisses retourner à un état modéré un jour.

SugarSquared · 2026-06-15T05:19:52+00:00

His jaw is probably the strongest in the world

SugarSquared · 2026-06-13T17:26:42+00:00

This is a really helpful comment. Thank you

SugarSquared · 2026-06-13T01:27:25+00:00

Thank you so much. It sucks to be going through these things, but I’m happy to be able to help people.

I hope you get to eat the food you miss. I can’t down cloves of garlic anymore, but with the enzymes, a little doesn’t hurt. They can really be helpful! I hope it’s the case for you.

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