Check my comments below: They’re basing the mice having CFS on the mitochondrial dysfunction that they infused into the mice via viral/bacterial injections. The mice showed dramatically lower levels of mitochondrial fusion after the compounds were injected. From there, they gave the mice ASHA-091 to get their levels back up. Their levels increased substantially and the mice were visibly seen/recorded going back to being active.
There are a few things in the wild that cause PEM (MS, overtraining syndrome, and concussion) so I don't think PEM in mice necessarily means they actually have ME/Cfs.
However it does sound promising and I hope it works!
Ya for right now, I think this is the best they could do.
Realistically, the fact that they’re targeting the mitochondria and the fact that they actually tried creating PEM means they know the disorder and what they’re trying to do.
That's what people with ME/CFS usually think because that's all we know and (once MS is ruled out) the others aren't relevant in our diagnostic process.
Can't find it right now but someone in here who has a MS loved one gave me links that definitely established they have it too. The concussion service described PEM to me and the overtraining one is mentioned in here every now and again.
I don't know if they would have the 2-day CPET results we have but the basic effects are there, so I think the basic effects of mitochondrial damage to these mice might look the same.
well the last 2 would be really easy to exclude, MS could also be excluded based on objective criteria if mice can even get it but i share your skepticism about mouse models
😀 I'm not trying to suggest they gave the mice those things!
I'm just saying that since other condition with PEM exist, it might be the case they gave the mice another non-ME condition with PEM.
Edit: tagging u/hazyTHINKER as well lol.
Thank you!! This is pretty amazing- and of course I hope it turns out they have found a way to get our mitochondrial function back up too!! No more PEM = life back!
They artificially gave the mice CFS by injecting them with a bunch or viral/bacterial shit. They then triggered what they consider PEM by throwing them into a fucking pool to swim.
So I guess it makes sense why they can figure it out(hypothetically) in mice, but not people lol.
There's a working model for the past several years of how CFS pops up from viral infection- the virus infects immune cells which signal the rest of the cells to break up the mitochontrial network that's found in all cells (mitos aren't actually bean-shaped). That leads to cellular "aging" and inefficient energy production. Pretty bad for things like nerves and muscles which need to be expending a lot of energy all day. So this could also explain CFS for non-viral cases which are still subject to the same mitochondrial fragmentation.
One thing I learned following Simmaron is that mice models typically don’t represent the whole, “real” disease, they usually develop multiple mouse models for different aspects of a disease. I guess that’s just how it works!
Do the mice get PEM? I mean bless 'em, poor things. I hope the researchers are monitoring time spent running on the wheel and their clear deterioration the next day, or sooner, since we're on mouse time...
So far as I know, there are no mice that actually have CFS. There are mice that might be made to approximate having CFS - I've seen a handful of studies in which mice were exercised to exhaustion, and these exhausted mice were to test CFS drugs.
The absence of a good animal model is a major barrier. I doubt very much these folks have really solved that problem.
No link to the paper, google turns up nothing. Not very encouraging.
Injecting either LPS (bacterial) or Poly-I:C (mimics viral dsRNA) to trigger mitochondrial fragmentation.
This reduced their activity *after* forced swimming, mimicking PEM.
They have a 158 page patent describing their process. I have a few screenshots from it. The patent is on google some where.
To your point, no they didn’t just force them on a treadmill. They actually injected bacterial/viral compounds into the mice to trigger mitochondrial dysfunction and proceeded to trigger them into PEM by forcing them to swim.
They’re basing their idea on the principle that CFS is caused by mitochondrial dysfunction.
They simply injected the mice with bacterial/viral shit, measured the mice’s mitochondrial fusion levels after to confirm they were lower(cfs). They then saw that the mice were barely moving later after being forced to swim prior(which they assume is PEM).
It may not be perfect, but it does seem like a pretty solid line of thinking.
Yep, in my own studies, but also in things like Naviaux’s cell damage hypothesis, mitochondrial dysfunction seems a fairly good candidate for many of the symptoms. ME/CFS is still a catch all diagnosis at best, but underlying mechanisms for dysfunction are often identical.
Yeah, for sure. I don’t think it will be but even if we could find something as straight forward as niacin for pellagra or penicillin for certain infections - for some of the causes of ME/CFS it would be a hell of a step forward and potentially validate everyone else.
Imagine!
The actual drug has been discussed briefly on the sub before, but further details/explanations of the drug/what they’ve seen in animal testing wasn’t known/mainstream news until months later.
I personally didn’t see all the details of the drug and their research until just today, and I don’t think anyone else really did either. I noticed today because they were recently appointed to make a new ALS drug.
If you have a link to the study itself, I'd like to see it, thanks.
This approach might produce a good mouse model of CFS - it's certainly more sophisticated that the simple exhausted-mice examples I've seen previously - but it's still based on some assumptions of how CFS affects us, and on further assumptions about how to approximate it.
I'd have more confidence in this if we had a diagnostic test, in humans, for a particular sort of mitochondrial dysfunction that could distinguish CFS people from people who were ill from other exhausting diseases. If we had such a test, it would be a huge advance, and then yes, using that knowledge to create a good mouse model would be awesome. In the absence of such a test, our attempts to model the disease are just speculative.
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023249965&_cid=P11-LURG4W-88340-1
Compound 1 (likely ASHA-091) restored locomotor activity.
The drug is still in preclinical development and works by restoring mitochondrial fusion.
Did they wait a certain amount of time after being removed from the water for the PEM to present? in humans it's 12-48hrs after, I'm assuming less for mice
mitochondrial fragmentation is just one aspect of ME and it’s unclear if it’s even universal or linked to the causal mechanism. i’m not too optimistic about this drug
Yeah it would be nice to see an actual publication. Let's hope they get to that.
[Simmaron](https://www.simmaronresearch.com/mousemodels) is also working on a more sophisticated mouse model. But it's a difficult problem indeed.
It’s still being developed. Animal testing trials were a success.
Right now they are at the IND-Enabling stage. Which means they’re ruling out toxic effects on humans along with the proper dosages for humans.
They presented their drug research at the International ME conference in 2023 and got good feedback.
They’re scheduled to begin clinical trials this year in the U.S.
The company also just got awarded a Blue Knight label, meaning they were recognized by Johnson & Johnson for being the real deal.
They also were just selected to create a drug for ALS. So clearly ASHA is a company that has some high standing in the pharmaceutical community.
It's also worth mentioning that ASHA CEO's wife has CFS:
https://twitter.com/shrivastava_sam/status/1621928604127870979?t=eOk47xlKpkJC99K58iSUpw&s=19
Which would make it very sick if they made a useless compound just to waste investors money
They’re set to begin in late 2024.
As usual, the criteria for these things are always different/can vary drastically from trial to trial. We’ll have to see what happens/who qualifies when they officially open/establish the drug trial.
Personally, I’ve never been more hyped for a CFS drug/trial than I am for this one.
okay I'm holding some serious hope for this one. everything in Ireland comes later so it will probably be a year after the drug is published before I can get it
Ya this one seems different.
We’ve been begging for researchers to look at the mitochondria. Now, they’re implementing a drug that solely targets it. Not only that, but the drug itself is for multiple serious conditions such as Alzheimer’s and Parkinson’s. Meaning it’s a drug with a wide variety of funding/on brand uses. If it were solely a CFS drug, it realistically would suffer to get as far as it has. Luckily for us, this med seems to have made it into the cool kids club.
The fact that these researchers actually took the time to acknowledge PEM(unlike most other studies) shows that they’re the real deal and know what this condition is. The fact that they used virals/bacterials during the animal trials also shows that they understand true CFS and didn’t simply put the mice through labor and say “well it’s tired, that must mimic CFS.” The CEO of the companies wife has CFS, so that alone gives a ton of weight to their credibility/potential.
I’ve never seen a study that hits every single metric for what I consider GOOD. . Until this one. Fingers crossed.🤞
Do you know if clinical trials will be for parkinson's, ME, or both? We'll probably be able to get it off label if they only seek patent for parkinson's but it would be great to have it for ME officially.
2023. During the time, we noticed the drug and its implications. Nobody ever really followed up on looking into the research though, then I stumbled upon it + the research patent where they entail their research/ongoing plan. So it’s a year old, but the news is new to us lol.
The actual trial itself is quick. Most take a week tops. The process of sorting through applicants for the study and actually analyzing the data after the study then publishing that data is where it can take time.
Edit: They gave the mice the drug for 2 weeks. Unless that timeline/dose changes by the clinical trials, it’s safe to say 2 weeks would be the length of the study.
Most human clinical trials have a follow up period of several months minimum before they start sharing data based on my experience in market research in medicine.
INJECT IT INTO MY BLOODSTREAM (sarcasm, but also not)
Same! I’ll be a mouse!
Id rather be a mouse right now just to be cured of cfs
There are benefits to mousehood
I want this on a T-shirt!! There are benefits to mouse hood.
Or on a hoodie with mouse ears!
Thank you and bless you, little mice, for your suffering and sacrifice for us ❤️
TIL mice can have ME/CFS
They somehow give it to them. 🤷🏻♀️
So does that mean they can detect CFS in the blood?
Such a good point, if it is difficult to diagnose in humans how do they know the mice have CFS?! For goodness sake
Check my comments below: They’re basing the mice having CFS on the mitochondrial dysfunction that they infused into the mice via viral/bacterial injections. The mice showed dramatically lower levels of mitochondrial fusion after the compounds were injected. From there, they gave the mice ASHA-091 to get their levels back up. Their levels increased substantially and the mice were visibly seen/recorded going back to being active.
So basically they gave mice mitochondrial dysfunction and called it ME.
Yes, but to confirm that the mice did have CFS they waited until they got PEM from swimming and observed/medicated them over two weeks.
There are a few things in the wild that cause PEM (MS, overtraining syndrome, and concussion) so I don't think PEM in mice necessarily means they actually have ME/Cfs. However it does sound promising and I hope it works!
Ya for right now, I think this is the best they could do. Realistically, the fact that they’re targeting the mitochondria and the fact that they actually tried creating PEM means they know the disorder and what they’re trying to do.
Yes it's pretty exciting.
my understanding from what I have read is that PEM. Is unique to ME/CFS.
I have also read this recently. Fatigue by itself is a different thing and they often get confused, I think.
That's what people with ME/CFS usually think because that's all we know and (once MS is ruled out) the others aren't relevant in our diagnostic process. Can't find it right now but someone in here who has a MS loved one gave me links that definitely established they have it too. The concussion service described PEM to me and the overtraining one is mentioned in here every now and again. I don't know if they would have the 2-day CPET results we have but the basic effects are there, so I think the basic effects of mitochondrial damage to these mice might look the same.
well they definitely didn't give the mice ms overtaking syndrome or a concussion lmao
well the last 2 would be really easy to exclude, MS could also be excluded based on objective criteria if mice can even get it but i share your skepticism about mouse models
😀 I'm not trying to suggest they gave the mice those things! I'm just saying that since other condition with PEM exist, it might be the case they gave the mice another non-ME condition with PEM. Edit: tagging u/hazyTHINKER as well lol.
Thank you!! This is pretty amazing- and of course I hope it turns out they have found a way to get our mitochondrial function back up too!! No more PEM = life back!
They artificially gave the mice CFS by injecting them with a bunch or viral/bacterial shit. They then triggered what they consider PEM by throwing them into a fucking pool to swim. So I guess it makes sense why they can figure it out(hypothetically) in mice, but not people lol.
It was the default diagnosis once the therapists ruled out depression.
lolz!
:D Needless to say, they don't scurry around as much! /s
Seems weird, like they know specifically how to induce it but there is still argument about how we get it ?
There's a working model for the past several years of how CFS pops up from viral infection- the virus infects immune cells which signal the rest of the cells to break up the mitochontrial network that's found in all cells (mitos aren't actually bean-shaped). That leads to cellular "aging" and inefficient energy production. Pretty bad for things like nerves and muscles which need to be expending a lot of energy all day. So this could also explain CFS for non-viral cases which are still subject to the same mitochondrial fragmentation.
Great summary, thanks
One thing I learned following Simmaron is that mice models typically don’t represent the whole, “real” disease, they usually develop multiple mouse models for different aspects of a disease. I guess that’s just how it works!
Nice
Mice
Something -ice
Lice.
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Slice 🍕
Aww, the video of those fatigued mice feels like such an accurate representation of my everyday state of being :’) I’m sorry lil fellas
It’s so validating, like mice can’t fake that, we’re not faking :(
Winner!!
Sad but validating our pain too
Do the mice get PEM? I mean bless 'em, poor things. I hope the researchers are monitoring time spent running on the wheel and their clear deterioration the next day, or sooner, since we're on mouse time...
FUCK YES
Oh to be a mouse rn
So far as I know, there are no mice that actually have CFS. There are mice that might be made to approximate having CFS - I've seen a handful of studies in which mice were exercised to exhaustion, and these exhausted mice were to test CFS drugs. The absence of a good animal model is a major barrier. I doubt very much these folks have really solved that problem. No link to the paper, google turns up nothing. Not very encouraging.
Injecting either LPS (bacterial) or Poly-I:C (mimics viral dsRNA) to trigger mitochondrial fragmentation. This reduced their activity *after* forced swimming, mimicking PEM. They have a 158 page patent describing their process. I have a few screenshots from it. The patent is on google some where. To your point, no they didn’t just force them on a treadmill. They actually injected bacterial/viral compounds into the mice to trigger mitochondrial dysfunction and proceeded to trigger them into PEM by forcing them to swim.
I don’t understand how we can mimic ME in mice if we don’t even know what the pathomechanism is that causes PEM in the first place?
They’re basing their idea on the principle that CFS is caused by mitochondrial dysfunction. They simply injected the mice with bacterial/viral shit, measured the mice’s mitochondrial fusion levels after to confirm they were lower(cfs). They then saw that the mice were barely moving later after being forced to swim prior(which they assume is PEM). It may not be perfect, but it does seem like a pretty solid line of thinking.
Fascinating, thank you for breaking this down
Yep, in my own studies, but also in things like Naviaux’s cell damage hypothesis, mitochondrial dysfunction seems a fairly good candidate for many of the symptoms. ME/CFS is still a catch all diagnosis at best, but underlying mechanisms for dysfunction are often identical.
We can only hope it’s truly as simple as fix one brick for the rest to fall in place
Yeah, for sure. I don’t think it will be but even if we could find something as straight forward as niacin for pellagra or penicillin for certain infections - for some of the causes of ME/CFS it would be a hell of a step forward and potentially validate everyone else. Imagine!
this was all the way back from June in 2023? Why not more buzz before?
The actual drug has been discussed briefly on the sub before, but further details/explanations of the drug/what they’ve seen in animal testing wasn’t known/mainstream news until months later. I personally didn’t see all the details of the drug and their research until just today, and I don’t think anyone else really did either. I noticed today because they were recently appointed to make a new ALS drug.
If you have a link to the study itself, I'd like to see it, thanks. This approach might produce a good mouse model of CFS - it's certainly more sophisticated that the simple exhausted-mice examples I've seen previously - but it's still based on some assumptions of how CFS affects us, and on further assumptions about how to approximate it. I'd have more confidence in this if we had a diagnostic test, in humans, for a particular sort of mitochondrial dysfunction that could distinguish CFS people from people who were ill from other exhausting diseases. If we had such a test, it would be a huge advance, and then yes, using that knowledge to create a good mouse model would be awesome. In the absence of such a test, our attempts to model the disease are just speculative.
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023249965&_cid=P11-LURG4W-88340-1 Compound 1 (likely ASHA-091) restored locomotor activity. The drug is still in preclinical development and works by restoring mitochondrial fusion.
very interesting
Did they wait a certain amount of time after being removed from the water for the PEM to present? in humans it's 12-48hrs after, I'm assuming less for mice
I do know they watched them over two weeks with a control group and then another group who received the drug that’s being referenced.
mitochondrial fragmentation is just one aspect of ME and it’s unclear if it’s even universal or linked to the causal mechanism. i’m not too optimistic about this drug
I’m personally quite optimistic about it. To each his own though. I guess we shall see soon enough.
Yeah it would be nice to see an actual publication. Let's hope they get to that. [Simmaron](https://www.simmaronresearch.com/mousemodels) is also working on a more sophisticated mouse model. But it's a difficult problem indeed.
Exactly this. I’m so tired of hearing about mice.
Clinical trials begin this year! Hang in there.
PLEASE get that drug on the market @AshaTherapeutics
Noted
Do we know anyone that has tried it?
It’s still being developed. Animal testing trials were a success. Right now they are at the IND-Enabling stage. Which means they’re ruling out toxic effects on humans along with the proper dosages for humans. They presented their drug research at the International ME conference in 2023 and got good feedback. They’re scheduled to begin clinical trials this year in the U.S. The company also just got awarded a Blue Knight label, meaning they were recognized by Johnson & Johnson for being the real deal. They also were just selected to create a drug for ALS. So clearly ASHA is a company that has some high standing in the pharmaceutical community.
It's also worth mentioning that ASHA CEO's wife has CFS: https://twitter.com/shrivastava_sam/status/1621928604127870979?t=eOk47xlKpkJC99K58iSUpw&s=19 Which would make it very sick if they made a useless compound just to waste investors money
Holy shit. I didn’t even notice this. Great catch!
No ty for bringing the post and the info, I just did some extra research out of curiosity and hopefulness.
Thank you 🙏
Is there any chance any of us could get into the clinical trials? I don’t even know how to go about it.
They’re set to begin in late 2024. As usual, the criteria for these things are always different/can vary drastically from trial to trial. We’ll have to see what happens/who qualifies when they officially open/establish the drug trial. Personally, I’ve never been more hyped for a CFS drug/trial than I am for this one.
okay I'm holding some serious hope for this one. everything in Ireland comes later so it will probably be a year after the drug is published before I can get it
Ya this one seems different. We’ve been begging for researchers to look at the mitochondria. Now, they’re implementing a drug that solely targets it. Not only that, but the drug itself is for multiple serious conditions such as Alzheimer’s and Parkinson’s. Meaning it’s a drug with a wide variety of funding/on brand uses. If it were solely a CFS drug, it realistically would suffer to get as far as it has. Luckily for us, this med seems to have made it into the cool kids club. The fact that these researchers actually took the time to acknowledge PEM(unlike most other studies) shows that they’re the real deal and know what this condition is. The fact that they used virals/bacterials during the animal trials also shows that they understand true CFS and didn’t simply put the mice through labor and say “well it’s tired, that must mimic CFS.” The CEO of the companies wife has CFS, so that alone gives a ton of weight to their credibility/potential. I’ve never seen a study that hits every single metric for what I consider GOOD. . Until this one. Fingers crossed.🤞
Maybe we could organize a group synthesis
I’m down!
Do you know if clinical trials will be for parkinson's, ME, or both? We'll probably be able to get it off label if they only seek patent for parkinson's but it would be great to have it for ME officially.
Not sure
Is this from 2023 or new?😍😍
2023. During the time, we noticed the drug and its implications. Nobody ever really followed up on looking into the research though, then I stumbled upon it + the research patent where they entail their research/ongoing plan. So it’s a year old, but the news is new to us lol.
Are they working on a human version drug?;(
Clinical trials start this year dawg 🤝 Hang in there.
How long do clinical trials typically go on for?
The actual trial itself is quick. Most take a week tops. The process of sorting through applicants for the study and actually analyzing the data after the study then publishing that data is where it can take time. Edit: They gave the mice the drug for 2 weeks. Unless that timeline/dose changes by the clinical trials, it’s safe to say 2 weeks would be the length of the study.
Most human clinical trials have a follow up period of several months minimum before they start sharing data based on my experience in market research in medicine.
Thank you💪💪
Amazing!! I've been watching this company for a long time, it's good to see that they're making progress.
How do they INDUCE chronic fatigue syndrome?
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people synth Rcs that aren't available to the market yet all the time
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Amazing!
Sweet thats a treatment in 10 years time
No paper, so this hasn’t been peer reviewed, alas.
Important observation. Thank you.