Animal Models of ME/CFS

They'd better get in quick before it's 'cured' using LP or CBT/GET, as will be easily determined by it getting a different, or the same, SF36 score than it manages the first time.

Possibly that in itself could be a cure, scurrying around on SF36 forms with inky paws?

(Then all we'd need is surgery to give us paws and we'd be 'cured')
 
@Simone I know this is not about a mouse model of ME/CFS but here is an excerpt from the 2018 Stanford Symposium about possibly modelling the IDO metabolic trap in cells and the different ways you can perform an experiment not easy to do in humans.
Now, the other problem we have is that we want to do some modeling and what I mean by modeling is we want to try to see if we can reproduce this in cell culture. What happened in our working group meeting the last three days is one of the scientists I invited said, “Heck I will make a yeast model for this. It's going to be really easy, all I’ve got to do is take out the genes from yeast to do this and replace them with the human genes.” That's actually pretty easy to do and it's very likely that they'll work. Then someone else came up to me and said, “I'll make a model of this in the nematode, all I’ve got to do is convince a graduate student to do it.” [laughter] That's easy right. Then another person at the meeting said I'll make a mouse model. That's what getting these people together means and those can speed up the experimentation, because it's hard to experiment on people but one of the components that we need is kynurenine, not easy to find and it's not been tested in human use.
Click to expand...
Source : https://www.omf.ngo/wp-content/uploads/2018/11/Edited-Ronald-W-Davis-Whats-Next.pdf

The OMF had a Livestream of Millions Missing San Francisco recently in May of Ron Davis talking about various topics and he said that that week he had just hired a scientist to work on yeast and if I remember right to test drugs and create compounds (some of which are produced by bacteria in the gut). I wonder if he will also look at modelling the IDO trap in yeast as was brainstormed? I thought there was a post on his MillionsMissing talk somewhere but I can't find it. H
 
Last edited:
wigglethemouse said:
Did someone say Mouse? Did you call me? Please don't experiment on me!!!!!!

@Simone the closest I can think of is Gulf War Illness which presents clinically very similar to ME/CFS and where the disease trigger is known. They have injected mice with the same "cocktail" that the 1990 Gulf War troops received and have observed similar illness behaviours. Something for your researcher contact to look into.

I believe one of the ingredients in the cocktail was mestinon, a drug that Systrom is trialing in ME. Of course there were others more toxic, but the combination from the cocktail likely caused multiple immune and CNS "hits" at the same time. It is thought that one third of folks sent to the 1990 Gulf War are now sick ~ 250,000 folks.
Click to expand...

Thanks, @wigglethemouse. I’m not familiar with that Gulf War research. Do you happen to know any of the researchers, so I can look it up?
 
@Simone Here is the Klimas mouse reference for ME/CFS from Dec 2018
Animal Modeling in ME/CFS

Due to the generosity of Kathy and Ron Assaf, who graciously hosted a fundraiser in their beautiful home, we have a starter fund to establish the animal model for ME/CFS as we currently do not have one in place.

This model is progressing nicely; particularly as creating an animal model is technically difficult. We must design a model that accurately mimics the inciting infection or exposure in the mouse, and also add in gender, which plays a large role in the effects of the illness in ME/CFS.

The complexity of the needed mouse model is the reason that we are 30 years into this work and we still do not have the necessary ME/CFS mouse model!
Click to expand...
Thread : https://www.s4me.info/threads/donating-to-klimas-clinical-trial.7330/#post-132288
 
I feel sure that there must be similar post-infectious fatiguing illnesses in animals; it seems highly unlikely that humans would be special in this. If we could find just one, it could give us an animal model.

There's this 2021 report about a ferret model for Covid-19 -
Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity
This ferret model of intranasal SARS-CoV-2 infection presents three key measurable endpoints: (a) consistent URT viral RNA shedding; (b) detectable lung pathology; and (c) post viral fatigue.
Click to expand...
They didn't actually identify anything like ME/CFS, but they had small samples and (despite what they say above) they weren't actually looking for 'post viral fatigue' - I think they just think that they can assess it. They were assessing alertness and playfulness. Also, they assessed ruffled fur, as apparently a sick animal stops grooming itself. There are also ways to assess how active animals are.

I wonder if any Covid-19 researcher using animal models has looked for PVFS so far. I've sent this team an email.
 
Last edited:
I've been searching to see if anyone has been looking at Long Covid with animal models. I haven't found any so far, but this paper at least acknowledged that it will be something to prioritise once vaccines are rolled out.

Animal models of COVID‐19 hyper‐inflammation, 2020
Finally, at a time when the first COVID‐19 vaccines are reaching advanced phases of clinical trials and manufacturing, efforts to model the long‐lasting impacts of SARS‐CoV‐2 infection should become a priority for the scientific community, as these will likely have significant burden on health systems for many years to come.
Click to expand...
 
The more I think about this, the more I am sure that ME/CFS must affect animals. It seems unlikely that a whole lot of diseases, as diverse as bacteria and virus can seem to trigger ME/CFS in humans without there being similar post-infection things going on in at least some animals. There are a whole range of coronaviruses that affect animals for example.

The problem is, how to identify such cases? Animals with ME/CFS in the wild are likely to be predated. Many pets lie around all day as it is; they may not face physical stresses that make ME/CFS obvious, and owners may just assume that the animal is lazy or getting old. It may not be investigated, and, if it is and nothing is easily found, investigations might stop (in much the same way as they do with us), and never be reported.

It seems to me that the easiest way to identify ME/CFS in animals is to talk with vets treating production animals or animals used in high-performance roles. So, I think vets treating dairy cattle, racing horses, racing greyhounds, sled dogs and the like might have some ideas, especially after outbreaks of novel infections. A problem of course is that often such animals will be killed fairly quickly, and the chronic lethargy might be put down to tissue damage without a whole lot of investigation. Zookeepers and zoo vets looking after primate colonies in zoos might have noticed something.
 
Hutan said:
The more I think about this, the more I am sure that ME/CFS must affect animals. It seems unlikely that a whole lot of diseases, as diverse as bacteria and virus can seem to trigger ME/CFS in humans without there being similar post-infection things going on in at least some animals.
Click to expand...

I am not so sure. A whole lot of infections trigger Reiter's syndrome in humans but I am not aware of Reiter's being described in animals. Interestingly the closest thing to Reiter's in animals is a disease produced by making rodents transgenic for one particular human HLA allele - B27. And of course ankylosing spondylitis is not just unique to humans it is pretty much unique to humans carrying HLA-B27.

The problem about asking vets is that most of them make diagnoses on the hoof (so to speak) on the basis of even less evidence than physicians. No animal is likely to go through all the tests needed to exclude other causes of whatever PEM might look like in that species.

One or two vets are very astute about pathogenesis. David Bennett took an interest in autoimmune rheumatic disease and studied lupus in certain breeds of dog - but because lupus is only found in one or two breeds. Most dogs never get it.
 
It is possible that ME/CFS is specific to humans, although, if there really are subsets of ME/CFS, then that makes it even less likely that all the versions of ME/CFS are unique to humans. If, as seems possible, pathogens are altering the host's immune system in order to make the environment conducive to their ongoing existence and replication, I think it's really unlikely that the pathogens are only using that strategy in humans. Even if ME/CFS is just an unfortunate consequence of a pathogen going about its business that confers no advantage to the pathogen, there are animals that are a lot like us that suffer from infections of some of the same pathogens.

Even if ME/CFS is a psychosomatic disease, I would expect it to occur in at least the higher primates. Many animals experience horrendous trauma. Humans aren't as special as we often like to think.

Jonathan Edwards said:
The problem about asking vets is that most of them make diagnoses on the hoof (so to speak) on the basis of even less evidence than physicians. No animal is likely to go through all the tests needed to exclude other causes of whatever PEM might look like in that species.
Click to expand...

Sure, lots of vets just go through the motions, as do many doctors. But many have facilities in house to analyse blood tests immediately, and they use them routinely. When our dogs got anaplasma infections, it was diagnosed immediately by the vet in Borneo, who looked at the blood under a microscope. It took me well over a year of campaigning after getting ME/CFS to be tested for anaplasma - my doctor in Australia had not previously heard of it.

Yes, animals won't get put through loads of tests, but if 10% of a dairy herd was struggling to walk to the milking shed for 6 months, that would be enough to prompt quite an investigative effort. There's the example of the 'Go slow' illness in dogs identified by a vet.

The global One Health movement aims to have scientists and clinicians of all sorts talking to each other more to reduce the risks from infectious diseases. In googling for this post, I see that one of the members of the NZ One Health group is interested in Long Covid
One of the few New Zealand researchers studying long Covid is respiratory physician and senior lecturer in medicine at the University of Otago Dr Michael Maze.
He and his team have been following people in the Canterbury region who caught the virus during the first wave of the pandemic in order to assess their recovery.

While the research is still in its early stages, he said Covid is a real phenomenon and Covid-19 survivors are suffering all over the world.

"I think we certainly are seeing that there are plenty of people out there who are telling us that they still haven't recovered," he said.

"I think the pattern that you're seeing overseas, with a proportion of people - 10, 20, 30 percent - who don't seem to be recovering three months, six months after the illness, we're seeing a similar pattern in New Zealand.

"What we don't yet know I think is truly what proportion is really incapacitated versus [those who are] not quite better but they're definitely getting better.
Click to expand...

I think that getting vets to consider the issue increases the chances that some clues come to light. Maybe Dr Michael Maze might be able to help - I'll try to talk to him.
 
Last edited:
Hutan said:
Even if ME/CFS is just an unfortunate consequence of a pathogen going about its business that confers no advantage to the pathogen, there are animals that are a lot like us that suffer from infections of some of the same pathogens.
Click to expand...

But I think the evidence shows that this does not turn out to be relevant. The best known chronic sequel of infection in humans in Reiter's and only a small percentage of even humans appear to have the immune equipment necessary to generate the illness. Similarly, I believe it is now considered that 90% or so of humans are incapable of getting multiple sclerosis. You have to have certain gene alleles even to have a chance of getting it.

My understanding is that a lot of the chronic conditions involving immune and nervous systems in humans relate to built in 'bugs' in complex regulatory software and are specific to our species and most often to genetic subsets of our species only.

It is also highly likely that some of these chronic illnesses have survived in humans because of our social support network. If they occurred de novo in wild animal populations the negative survival impact would be likely to clear them from the population in a few generations. In the days when I modelled disease causation I reckoned that for diseases with a mixed polygenic/stochasitc aetiology, which applies to a lot of autoimmune disease the tolerated rate for a chronic illness would be likely to be no more than 1:1000 to 1:200 in humans. For wild animal species I think it would be less so pretty hard to find. Diseases tend to get recognised in domestic animals when they have been bred in to inbred pedigree populations - like hip dysplasia in labradors and lupus in King Charles spaniels.
 
You must log in or register to reply here.
Back
Top Bottom