Author Patrick Ussher undertook to understand the latest research in order to cope with his daunting health challenge

[southwestforests]

Just saw this via a Tumblr post by an Irish guy who has ME/CFS.
The post,

https://myalgicencephalomyelitiscfstom.tumblr.com%2Fpost%2F791116254570250240

Direct link to newspaper article mentioned in post,
https://www.irishtimes.com/health/y...lanation-for-this-long-misunderstood-illness/

Now, in his book, Understanding ME/CFS & Strategies for Healing (2025), Irish author Patrick Ussher not only adds compelling insights to the burgeoning evidence base for ME’s physical origins, but also outlines a unifying model for ME, highlighting research towards possible effective treatment.

He adds: “For ME to make sense as an illness, it cannot be random: it must follow certain physiological laws.”

These physiological laws inform the evolution of Wirth and Scheibenbogen’s unifying model hypothesis, which inter alia considers a key role for autoantibodies against blood flow-related cellular receptors in skeletal muscle and the brain; the mechanisms by which ME patients develop low blood volume and systemic blood hypoperfusion (a reduced amount of blood flow); and the contribution of high muscle sodium and calcium concentrations to mitochondrial dysfunction and muscle-tissue necrosis.

The refinement of Wirth and Scheibenbogen’s unifying model hypothesis has led to a therapeutic concept: a drug called Mitodicure, which is “a novel molecule to treat patients with exertional intolerance and post-exertional malaise (PEM)”. Steps are under way to attract funding for clinical trials.

Mitodicure, says Ussher, “could represent the long-awaited breakthrough treatment for ME and Long Covid. Its mechanism of action will interrupt several key vicious cycles at once, particularly targeting the mechanisms underlying PEM.

“During symptom exacerbations of PEM,” he explains, “most illness mechanisms heighten and intensify. By preventing PEM, Mitodicure could relieve physiological burdens, enabling the body to concentrate its resources on healing.

“Mitodicure is not symptom suppression,” Ussher emphasises, “Prof Wirth considers Mitodicure to represent a potential cure for these illnesses.”

Cautiously optimistic, Ussher suggests that Mitodicure could demystify ME: “If you have a therapeutic based on a certain disease model and it works as hypothesised, the disease model is also validated. The pill can prove the principle. So Mitodicure could offer not only improved quality of life (or better) but could also advance our understanding of ME.”

Although Ussher’s enthusiasm is tempered with an acute awareness of the need for scientific rigour, his approach to science appears sceptical towards the exalted status of stored facts and may align with Mary Midgley’s view that stored facts are “valueless unless you know how to use them, how to connect them with other things, how to understand them”. Ussher’s book represents an interpretative scheme; a vehicle, as he puts it, “for raising awareness of Wirth and Scheibenbogen’s ‘unifying model’ of ME and the potential Mitodicure pill which is based on it”.

 

[Wishful]

I managed to cure my PEM, but didn't cure my ME, so I don't see blocking a PEM mechanism as a cure for ME.

 

[Mary]

I managed to cure my PEM, but didn't cure my ME, so I don't see blocking a PEM mechanism as a cure for ME.

@Wishful - what are your ME symptoms?

ETA: If I didn't have PEM, I think I could almost live a normal life . . . or perhaps I could -

I think curing PEM would be HUGE for just about everyone here -

 

[hapl808]

I think curing PEM would be HUGE for just about everyone here -

For me, PEM crashes destroy my life. They are completely and totally unmanageable. A 20 minute visit with a friend is multiple days of recovery. Even when I was 'mild', one full day of work required at least a full day to recover.

I have plenty of symptoms that might remain if that were the only thing fixed (constant headaches, brain fog, muscular issues, etc), but the difference to my quality of life without PEM would be indescribable.

I managed to cure my PEM, but didn't cure my ME, so I don't see blocking a PEM mechanism as a cure for ME.

Seeing as PEM is often thought to be a required symptoms of MECFS and since we don't really have great diagnostics, not sure if your remaining symptoms would still be called that or would need another name.

But pretty sure the Mitodicure thing has been around for a few years and doesn't sound like it's got any promising data or close to any trials? Not sure it gives me any hope.

 

[Rufous McKinney]

I have plenty of symptoms that might remain if that were the only thing fixed (constant headaches, brain fog, muscular issues, etc), but the difference to my quality of life without PEM would be indescribable.

same....PEM is the poison phase. But just the normal day, comes with the constant depreciations, fog and eye problems. The fog can be SO thick, as we try to swim through it.

Oh, yes and then there is if I try to go out for little while, THAT list of issues. (woozy, perilous, pathetic)

 

[Wishful]

@Wishful - what are your ME symptoms?

Mostly lethargy and brainfog. PEM used to make those worse. Now, various food intolerances make those symptoms worse. Are the food intolerances due to ME? Would whatever biochemical food effects exist but cause no noticeable symptoms if ME's mechanism wasn't operating? I have no idea.

I think curing PEM would be HUGE for just about everyone here -

Absolutely, and I can speak from actual experience of that. I was thrilled to be able to offer that cure for PEM for others. It's not my fault that no one else has responded to cumin the same way.

My comment was against the claim that curing PEM was a potential cure for ME. I cured my PEM (worsening of symptoms due to exertion) but that didn't cure my ME.

Maybe test mitodicure and cumin?

 

[Wishful]

Seeing as PEM is often thought to be a required symptoms of MECFS and since we don't really have great diagnostics, not sure if your remaining symptoms would still be called that or would need another name.

People don't suddenly develop a similar-except-for-one-criteria disease after curing the first disease. It's the same disease with an exception. In a system as complicated as the human body, you should expect exceptions, and some of those exceptions could block or bypass a symptom of a disease. Maybe PEM involves a molecule transferred by vesicles, and my specific vesicle-producing-equipment is different from standard, and allowed changes from cuminaldehyde.

The only noticeable change from taking cumin was that I didn't have my symptoms worsen 24 hrs after physical exertion. I still had PEM from cognitive exertion, so I still would have qualified by the ME criteria, but those criteria do not insist on physically-triggered PEM. If it's possible to cure one triggering type, it seems reasonable to accept that the other type can be cured too ... without it suddenly becoming a completely different disease.

I expect that when ME's mechanism is properly understood, the criteria will be updated to include no PEM.

 

[Mary]

. I still had PEM from cognitive exertion,

I have this - I think most of us here have PEM from cognitive exertion as well as PEM from physical exertion. it is a bit maddening - I don't have much of a social life and on the few occasions I do socialize at night, I'm bedridden the next day even if I'd done next to nothing else that day - e.g. a (board) game night will throw me in the bed the next day.

 

[pamojja]

I was thrilled to be able to offer that cure for PEM for others. It's not my fault that no one else has responded to cumin the same way.

Actually, cumin was a very tiny contribution to dozens more significant nutrients associated with my PEMs remission in 2018 too (both physical and cognitive).

I still had PEM from cognitive exertion, so I still would have qualified by the ME criteria, but those criteria do not insist on physically-triggered PEM.

Thanks for the clarification. Yes, with PEM from cognitive exertion, you of course still experience a kind of PEM, just more specific.

I managed to cure my PEM, but didn't cure my ME, so I don't see blocking a PEM mechanism as a cure for ME.

So please be more careful with your wordings. The cure-word, I would avoid, might just show not true in any time soon. But then remission of PEMs (from both physical and cognitive exertion), for all practical ends, is remission of ME/CFS. Unless we start to conflate 'chronic fatigue' from any other cause, to real ME/CFS.

 

[JES]

But this still sounds to me like very much a symptomatic treatment and not a cure. If you had a cure you wouldn't need to keep taking a medication to prevent worsening every time you decide to do an activity...

A cure according to their disease model would be to get rid of those autoantibodies or a step further, fix the immune dysfunction causing those autoantibodies to appear.

 

[I am sick]

Just saw this via a Tumblr post by an Irish guy who has ME/CFS.
The post,

https://myalgicencephalomyelitiscfstom.tumblr.com%2Fpost%2F791116254570250240

Direct link to newspaper article mentioned in post,
https://www.irishtimes.com/health/y...lanation-for-this-long-misunderstood-illness/

Hi
Did anyone read what was considered to be high Calcium level.
I looked way back to my earliest records to when I had a yearly physical and came across a change in mine.
My Sodium is always in the middle.

I do have kidney stones, calcium type
So I have always tried to keep my calcium containing foods limited.

In 2021 before I had omicron
HX CALCIUM
Normal range: 8.5 - 10.5 MG/DL
Mine was 7.8

July 17th 2025
Now it is the highest ever right after kidney stone surgey.
Mine 10.3

 

[southwestforests]

Hi
Did anyone read what was considered to be high Calcium level.

The other things going on with my body have been really roughing me up today, Sunday, I'm not good for conversation especially one which requires recalling data.
Thunderstorm approaching, may have to unplug computer stuff pretty quick.

 

[I am sick]

The other things going on with my body have been really roughing me up today, Sunday, I'm not good for conversation especially one which requires recalling data.
Thunderstorm approaching, may have to unplug computer stuff pretty quick.

Hi
I hope you are doing better !

 

[Wishful]

The cure-word, I would avoid,

Can you suggest a better term for a symptom disappearing and staying gone without further treatment? I couldn't think of a better term, so used "cure" even though I felt it wasn't quite appropriate.

But then remission of PEMs (from both physical and cognitive exertion), for all practical ends, is remission of ME/CFS. Unless we start to conflate 'chronic fatigue' from any other cause, to real ME/CFS.

No, it's absolutely not remission of ME; the lethargy and brainfog and other symptoms such as intolerances of foods and double-vision, were there before I used cumin, and still remain. It's not chronic fatigue, since it's not fatigue; it's fatigue-like. Normal fatigue feels different, and responds differently to factors such as rest.

I see PEM's mechanism as an extra input to ME's symptom generation mechanism. ME causes symptoms, and PEM's output feeds into ME's mechanism to increase those symptoms. My food intolerances have what seems to be the same effect. I wasn't able to tell the difference between eating a problem food or having done an activity that triggered PEM. I had to repeat the food or the activity to determine which was responsible for the increase in symptoms.

 

[pamojja]

Can you suggest a better term for a symptom disappearing and staying gone without further treatment?

Remission of symptoms is a much more approbate term. In cancer remission they talk about 'spontaneous' remissions, though in those cases mostly comprehensive life-style changes and supplementation were involved. After 5 years in remission, it's usually considered 'cured'.

No, it's absolutely not remission of ME; the lethargy and brainfog and other symptoms such as intolerances of foods and double-vision, were there before I used cumin, and still remain. It's not chronic fatigue, since it's not fatigue;

See, some argued my ME/CFS being only fatigue of chronic diseases (in my case PAD and COPD), as for example in the fatigue in cancer patients too. With PEMs ceasing 3 year later than those 2 chronic diseases, in my case it clearly met the criteria for ME/CFS. PEM was caused by physical or mental exertion, and always included body-pains, brain-fog and severe exhaustion for days after.

Food intolerances are a common part of ME/CFS, but alone is not considered ME/CFS. Double vision too.

Seeing brain fog and lethargy not as part in the fatigue of PEM, is beyond me, honestly. And of course could, if the sole remaining symptoms really without being fatigued, as well be symptoms of something completely else. Like food intolerances, which as the symptoms of PEM, could last for days.

You are free to consider yourself whatever disease label you want, of course. But assuming something which isn't anymore ME/CFS, puts yourself on a wrong track.

 

[Wishful]

After 5 years in remission, it's usually considered 'cured'.

Okay, then I cured my PEM triggering (7 years now).

Seeing brain fog and lethargy not as part in the fatigue of PEM, is beyond me, honestly.

I'm not sure what you mean by that. I try to avoid the use of "fatigue" for ME, since it's so poorly defined that it's misleading. Lethargy and brainfog are regular symptoms of my ME, and triggering PEM increased the severity of them; they weren't PEM-only symptoms.

 

[pamojja]

I try to avoid the use of "fatigue" for ME, since it's so poorly defined that it's misleading.

I don't think so. When young and healthy, I worked on construction sites, some days more than 12 hours a day. After such long days, I was fatigued and exhausted, had body pains and brain fog. Gone the next day, and ready for another 12-hour hardworking day.

PEMs are simple much more severe after ridiculously less exertion. Recovery with even the least amount of activity takes many days, never the next day.

Misleading I find rather the term 'chronic fatigue', since that by definition is not related to any acute mental or physical exertion, and indeed could be the result of any other chronic disease. In this case off course of ME/CFS too. But certainly not as sole criteria.

Lethargy and brainfog are regular symptoms of my ME, and triggering PEM increased the severity of them; they weren't PEM-only symptoms.

See, like the misleading term 'chronic fatigue' (since it could be a symptom of any chronic disease), lethargy or brain fog were not even part in my case of ME/CFS (mild; 50% disability), unless as side effects from real, for days-lasting PEMs. And again point to other co-morbidities, not necessarily defining ME/CFS.

Okay, then I cured my PEM triggering (7 years now).

As said, you are free to consider yourself what ever you want. But especially my encounter of so many expressions of ME/CFS with different outcome here on this forum, I consider symptomlessness for at least a year, a remission. And wouldn't be surprised if it came back in a blink of an eyelid.