Mouse models could rapidly increase our understanding and the development of treatment options for ME/CFS and allied diseases.
The thousands of mouse models that have been produced have played a critical role in understanding and developing drugs for diseases.
Guess which disease, though, does not have one? That’s right it’s ME/CFS. For 40 years it’s been missing a critical component of any disease infrastructure.
Currently, though, two mouse models are under development. You might think they must be coming from a major lab, but no. When Gunnar Gottschalk returned to Simmaron with his Ph.D. in hand, he brought with him Chief Scientific offer, Avik Roy, Ph.D.
Together, they’ve brought new vigor and creativity to this field – and are on their way to developing the first mouse model for ME/CFS – a model that is already producing potential insights regarding the energy production problems in this disease.
Find out more in
Seeing ME/CFS: Creating the First Mouse Models for the Disease
Cort, thanks for adding the link to SIMMARONRESEARCH.com article.
Quite a ‘wow’ that female mice were more fatigued:
“ Interestingly, the mice displayed a dramatic gender split with the female mice much more apt to display fatigue – a sign given the gender split in ME/CFS that they were on the right track. ”
Wow, I just read Brendan Rob’s ethical objection to creating a mouse model for ME/CFS on Simmaron. I live across the street from NIH in Bethesda, Maryland. The NIH campus is now almost as large as the University of Maryland at College Park, just down the road. The NIH labs are “busting at the seams” with mouse, rat, and cat models. The NIH will not address ME/CFS as an actual metabolic disease, because there is no bio-marker or “rat model”. The NIH will not even listen to prominent physicians like Dantini, Levin, and Teitelbaum, who all suffered from the disease for many years. I wish Brendan Rob could see the thousands of biochemists that pour into that place every morning. Then, think about how ME/CFS has been given only Nath’s team to “quiet us down”, and you would get nauseous. Something as important as “mitochondrial dysfunction” due to a viral infection, mold mycotoxins, gut dysbiosis, autoimmunity, etc., should be a priority. My neighbor’s NIH lab euthanizes more cats in a week while attempting to develop a drug to fight battlefield nerve gas, than mice that have ever died due to ME/CFS research. Take a look at Stanford genetics professor Dr. Davis’s son, and then tell me you are worried about mice. There are tens of millions of humans on this planet battling this disease. This disease is not just treatable, it is curable. Those of us that can work, pay the salaries and generous pensions of The Public Health Service. We must demand to be taken seriously. If their biochemists don’t want to do the work because the disease is too complicated, then “farm it out” to Klimas, Lipkin, Hanson, Montoya, Younger, et al. But, give them enough funding to get somewhere!
This is a big step let’s hope they find reliable biomarkers for ME in the not so distant future! Thank you Cort for all the great articles lately they give me a glimmer of hope although I wish we didn’t have to use animals obviously. I also agree that we need to push the women’s health advocacy as it is a big theme at the moment while also recognising that many men are affected.
I do feel for the mice and wish all the animals they use didn’t have to be sacrificed in this way. Frankly, when lack of an animal model is cited, it is just an excuse for denying more funding for ME/CFS. Shame!
Now, on to another tidbit; I recently read a series of anecdotical accounts of long Covid sufferers suddenly improving when given Paxlovid–yet so far nobody wants to fund a study on this. And then there was this; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233978/?report=classic
Basically approximately 66% of people with long Covid also had reactivated EBV virus! Researchers are hypothesizing that long lived viral fragments could be tweaking the immune system. Could this be happening in ME/CFS? I know there have been some trials of antivirals for us, but not with consistent results. Perhaps we haven’t found the right one?
One of the readers asked about my trial using Oxaloacetate. I now have been dosing at 800mg. per day and results, if there are any, are subtle. I have recently been trying additional supplements in an attempt to improve blood brain flow. These are Vincocetine and L-Arginine. So far I do notice some results.
Also have begun seeing a new doctor since I’m not so happy with Stanford’s efforts. This is through U.C.S.F. Integrative medicine. This new doctor is quite taken with dietary modifications and so I have started a new trial of an anti-lectin, non-dairy and gluten free diet. I hate it! Especially because I really haven’t had gastrointestinal symptoms excepting for the achalasia. Regardless, I will try and see if it helps.
She has also instructed me to take huge doses (grams) of NAC and Omegas. Pending a test for histamine, there are yet more supplements in the wings. I have just begun so the jury is out…
Nancy how do you know you need to improve your blood brain flow? DId you have any specific tests showing abnormal blood brain flow?
@Martin,
I haven’t had any test to determine my brain blood flow, but other researchers have alluded to this in ME/CFS. In addition, when you have POTS or another dysautonomia, the theory is that blood pools in the lower extremities and gives one symptoms like darkening vision, visual stars, dizziness–and brain fog. I have some of this and in addition I have trouble finding words–but it is not consistent. Some days are much worse than others.
In my own humble way, I researched what supplements might help–and then I try them. Honestly, it might not be brain blood flow at all, but something else (Inflammation?). The important part is–does something help?
Nancy B
Bhupesh Prusty has been working on EBV and has found interesting things over time about how EBV infected cells effect other cells. Especially regarding mitochondria of cells getting fragmented.
His Twitter has various studies he’s been involved in linked.
@Sunie,
Thanks for the info on Prusty!
Of course this leads to yet more questions as it is estimated that around 90% of people, at some point, have been infected with EBV. If that is true, why do some have later issues and why others do not? The list of comorbidities with EBV is getting longer. I worry that there is some big snarl of post viral fragments of various types, transforming over time, impacting our bodies–so complicated that it will be too difficult to completely figure out.
Ah, so many confounders!
What happened to the drug Ampligen which cured some people with CFS?
They are now using it in research against pancreatic cancer. With positive outcomes.
You missed my point. If ampligen cured some people with CFS, why aren’t they still using it for those types of people who benefit from it?
When I had CFS, all my tests were normal. No EBV/CMV, thyroid ok, no lyme, full blood count good, c reactive protein normal, serology normal, coxiella burnetii antibodies normal, R Nase L normal, and so on. everything normal. But I had cfs for around 16 years and then I recovered. Been OK now for 12 years and counting. Long covid is CFS now. so maybe they will find something but most things are normal.
Martin, may I ask what you attribute your recovery to?
I have no idea really. I just got better spontaneously without any medication. I was never bed bound though and could mostly work through the fatigue and other symptoms. Lasted 16 years though which I think is enough for anyone. I feel sorry for the people who have had it longer. I still wonder how I could have had those symptoms when everything came back normal.
How did you recover?
Martin did you have reduced stress?
@Martin (second response),
I, like many of you, have all normal labs–well, almost all normal. One of the big problems with this disease is that there are no definitive tests and that makes many doctors not want to recognize it as such. In one article it is identified as a ‘contested’ disease.
As far as Ampligen goes, another problem with ME/CFS is that since fatigue is such a common symptom of many disorders, at the moment it is very difficult to determine who might benefit from what. Remember when breast cancer was just breast cancer–but then with further research it was discovered just how many types of breast cancer there were? (Well, you being male might not identify with that…anyway…)
Since we can’t easily parse what type of ME/CFS a person may have, it is very difficult to try to match treatments. You may have had some subset of fatigue that has not yet been identified–hence your unusual and wonderful recovery.
We need much more research!
The Simmaron article mentions a clinical trial by Nancy Klimas, was that ever completed? Or was it a case of another failure?
A mouse model for ME? Seems complicated if not impossible to me. They mean fatigue that also occurs in other diseases. Has nothing to do with ME.
How can you make a mouse suffer from ME? We don’t even know what ME is. Running mice in a carousel to exhaust them has nothing to do with ME.
The only way to further investigate ME is to take biopsies of all organs alive and after death (brain).
Running a mice in a carousel and then now having it recover after its rested has possibly everything to do with ME/CFS. So does altering the mouse in a way that it can’t exercise anymore.
The study were Ron Tompkins and Ron Davis met/worked together for the first time – it was BIG, many teams all over the country looking at everything etc – showed that the immune response mounted by humans was quite different from the one in rodents. That is to say, there was no equivalency.
The use of mice seems ill-matched.
They are nocturnal animals, their metabolisms diff from us. They spend most of their time on all fours – maybe then not a good model for orthostatic issues biped humans have?
There was a study about how the temperature in labs is mostly cold, and this also affects their metabolism in particular ways. Plus the stress of being confined and the hands reaching in to grab them.
Sigh…
You know, researchers have been using mice for a long, long time. Whatever considerations you and I have about the differences between mice and humans has been assessed by research establishment again and again and again. Mice are used because they provide valuable insights. Do the differences between them and humans have to be taken into account? Obviously.
Have a read at these:
●”Why Drugs Tested in Mice Fail in Human Clinical Trials”
https://sitn.hms.harvard.edu/flash/2020/why-drugs-tested-in-mice-fail-in-human-clinical-trials/
“However, in complex neurological disorders where many genes are disrupted, mice are unlikely to model the disease correctly, making a cure for humans less likely. In these cases, some researchers suggest studying human cells in isolation and abandoning mice models.”
This sounds like Ron Davis’ approach – testing subtances on the [sick] ME/CFS cells using the device he invented.
Also:
● “Mice Are Telling Cancer Researchers: Give It Up”
https://www.pcrm.org/news/good-science-digest/mice-are-telling-cancer-researchers-give-it
“Where to from here? First, it’s long past time that we take notice of the many ways that mice have shown us that they are not tiny humans. Despite decades of research model manipulation, mice are no better at recapitulating the course or treatment responses of human cancers. Second, the logical transition to human-relevant cancer research methods is overdue. Whether the barriers to this transition are researcher arrogance, career and funding considerations, or regulatory restrictions, these must be overcome if the abject failure of mouse research for cancer is to be reversed.”
● “Mouse model of human immune system inadequate for stem cell studies”
https://www.med.stanford.edu/news/all-news/2017/08/mouse-model-of-human-immune-system-inadequate-for-stem-cell-studies.html
“Many in the fields of pluripotent stem cell research and regenerative medicine are pushing the use of the humanized mice to study the human immune response,” said Kooreman. “But if we start to make claims using this model, assuming that these cells won’t be rejected by patients, it could be worrisome. Our work clearly shows that, although there is some human immune cell activity, these animals don’t fully reconstitute the human immune system.”
There is more when you look for it.
Why would anyone expect mice “to fully reconstitute the human immune system”? I wouldn’t expect any animal to do that.
Nancy Klimas did extensive computer modeling of GWI – and then found the GWI mice recapitulated what the modeling indicated.
Yes, of course, there are limitations and researchers are trying to understand and work around those limitations.
https://www.hopkinsmedicine.org/institute_basic_biomedical_sciences/news_events/articles_and_stories/model_organisms/201010_mouse_model.html
Whatever their failings mouse models play a huge role in medical research. Research comes out virtually every day on potential discoveries made in mouse models.
https://www.bbc.com/future/article/20220422-the-quest-for-super-human-healing
https://www.medicalnewstoday.com/articles/covid-19-repurposed-antibiotic-shows-promise-in-mouse-model
What is the alternative? It would be great to have the nanoneedle but unfortunately, it’s stalled. It looks really good and there’s a lot we don’t know about it. I would not give up on what a mouse model could tell us in hopes of what the nanoneedle may tells us. I would keep working on both.