Could the Mitodicure Pill be the Long-Awaited Answer for ME/CFS and Long COVID?

Imagine if there were a medication that could make it very hard, even physiologically impossible, to crash. How much better might your quality of life be? Or might such a pill even facilitate recovery, given how post-exertional malaise (PEM) is such a barrier to healing?

Prof. Klaus Wirth is a man on a mission to create that pill. Previously a senior researcher at Sanofi, a leading pharmaceutical company, he pivoted his entire focus onto ME/CFS seven years ago.

The illness was initially entirely new to him, and he came across it only after watching a TV report about a young and bedridden ME/CFS patient. However, with a background in cardiovascular and cellular problems, many facets of the ME/CFS research were familiar to him, and he became determined to develop a comprehensive understanding of the illness.

Ultimately, his ambition became to create the world’s first ME/CFS pill. By this, I do not mean yet another ‘off label’ medication that might treat some peripheral aspect of the illness, but rather a medication that would actually target the core pathophysiology of the condition. And that would be a medication that could, therefore, make a real difference. If you know what the problem is, then you can actually treat it.

That potential medication is called Mitodicure, and I will tell you all about it later in the blog. But let us first gain a clearer understanding of the research on which it is based.

The Groundbreaking Collaboration of Professors Klaus Wirth and Carmen Scheibenbogen

Early on, Prof. Wirth teamed up with Prof. Carmen Scheibenbogen, who leads the ME/CFS clinic in the Charité University Hospital, Berlin. They sat down together to write a series of groundbreaking papers about ME/CFS.

These papers are groundbreaking because they take a whole new approach to the illness. Most of the ME/CFS research to date has focused on identifying problems in specific parts of the body. What’s going on in the heart, the blood vessels, the gut or the brain? This research has been necessary and advanced hugely our understanding of the illness, but in the end, we are left with many findings that can seem unrelated. In other words, all the problems can seem a bit random.  

Wirth and Scheibenbogen set themselves a different question: what can unite all the most important pre-existing findings in ME/CFS? How does X lead to Y and Z? How does one vicious cycle cause another? And are the vicious cycles ultimately all just parts of one big vicious cycle? In other words, they wanted to join up the dots.

Their subsequent 2020 paper was a real tour de force. Titled A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors, it mapped out a convincing model for how the core problems within ME/CFS interrelate. Further papers followed, including one on muscle disturbances and another on neurological impairment. Their research collectively offers a convincing model of ME/CFS, linking low blood volume, autoimmunity, cardiovascular complications and cellular-level effects.

That explanation is too complex to go into here, but we will focus on one part of their research, namely, dysfunctions in the skeletal muscle. For it is treating this problem, which Prof. Wirth believes might hold the key to dramatically improving the lives of ME/CFS patients (or perhaps healing the illness altogether). For both Wirth and Scheibenbogen, this dysfunction is ultimately responsible for post-exertional malaise, and if a medication could target that dysfunction, PEM could become a thing of the past.

What Is Post-Exertional Malaise?

Of course, a medication to make PEM impossible sounds like quite a big claim. Why does Prof. Wirth think this is possible?

For that, we need to ask ourselves what PEM is. The answer might shock you but put in the simplest possible terms…PEM is when your muscles die.

This was found in a fascinating study from the Netherlands by Appelman and Wust in early 2024. They performed biopsies of long COVID patients before and after an exercise challenge. They were then intrigued to see a high level of ‘necrotic muscle fibres’ (i.e., dead muscle fibres) in the patients once PEM had set in.

Now, the body will slowly regenerate muscle tissue, but this shows us that there is something about exercise which physically damages the muscles of the ME/CFS patient. In fact, ‘damages’ might be too weak a word. ‘Kills’ is clearly a better one, and, given how awful PEM can feel, well, perhaps we should not really be too surprised at this finding after all.

But what can explain this muscle tissue death? Remember, for ME/CFS to make sense as an illness, we need to be able to relate all its core problems to each other. Nothing can be random. There must be something in the pathophysiology of the condition that can explain why exercise can ‘kill’ muscle fibres. And Wirth and Scheibenbogen believe their model can explain exactly why this happens.  

How Wirth and Scheibenbogen Explain Post-Exertional Malaise (PEM)

To explain how, we need to take a little step back and first ask ourselves how muscles work when they are performing well. Then, we will be best placed to understand what is going wrong in ME/CFS.

Our body is comprised of 40 trillion cells. Within the muscles, healthy cellular functioning depends upon the correct concentrations of sodium and potassium inside the cell.

(Now, to be 100% clear: I am talking here about the concentration of sodium/potassium within the muscle cells themselves. I am not talking about their concentrations in the bloodstream, which you get measured in your bloodwork. The former relates to intracellular concentrations, the latter to extracellular concentrations.)

Simply put, muscle cells need to contain more potassium than sodium. The cell achieves this thanks to a little pump that sits on the cell wall. That pump is called the ‘sodium-potassium’ pump, and its job is to ensure that the cellular concentrations of sodium and potassium remain just as nature intended.

But in ME/CFS, this pump starts to become dysfunctional. It does so for a range of more ‘upstream’ illness mechanisms, but the upshot is that the pump’s activity slows down. And once it slows down, the cell starts to contain too much sodium.

This was confirmed in a breakthrough study by Wirth and Scheibenbogen in 2022. Using MRIs, they measured the muscle sodium content in ME/CFS patients and healthy (but sedentary) controls following some basic muscle strengthening exercises. Muscle sodium content will increase following such exercises anyway, but in this study, the muscle sodium content increased 30% in the ME/CFS group and only 17% in the controls. This proved a key pillar of the Wirth and Scheibenbogen model.

On its own, elevated muscle sodium content will make the muscles weak and easily fatigable. But it also sets the stage for a much more serious problem: excessive cellular calcium.

This is because, when the cell becomes overloaded with sodium, its ability to clear out calcium also becomes severely impaired. As a result, cellular calcium overload can occur.  Cellular calcium overload is a very serious state of affairs for the cell. It damages the mitochondria, can cause cell toxicity, and even cell death.

For Wirth and Scheibenbogen, the high cellular sodium concentrations mean that the ME/CFS patient is only ever one (false) step away from also experiencing cellular calcium toxicity. And, for them, cellular calcium toxicity is the central mechanism of PEM. In a 2021 paper, they write, “We assume calcium overload is the main mechanism of PEM, exercise intolerance and more severe relapses.”

In their model, calcium overload is also the cause of muscle death. This makes sense for, as I just mentioned, calcium overload can cause cell death.

In their most recent paper, Wirth and Scheibenbogen argue their case as follows (with some of my own explanations in brackets):

Based on our current knowledge on the known causes of muscle damage related to exercise and malperfusion (i.e., poor blood flow), diminished function of ion transporters (i.e., of the sodium-potassium pump) and consecutive calcium overload-induced toxicity is the only explanation for tissue necroses (i.e., muscle tissue death) and particularly mitochondrial damage in ME/CFS….Calcium overload cannot be demonstrated in vivo by imaging techniques, but the histological picture found in the biopsy study (i.e., of Appelman & Wust) after exercise, showing necroses, can only be explained by calcium overload.

So, there are strong reasons to think that the Wirth and Scheibenbogen model has demystified PEM. But what are the implications of this for future treatments?

Could Mitodicure Be the Breakthrough Pill to Treat ME/CFS and Long COVID?

Wirth believes that PEM is the key problem to eliminate. This is because PEM always heightens and intensifies the central illness mechanisms and represents a major ‘repair job’ for the body on each occasion of its triggering. He compares PEM to the gearbox of a car, writing: “The patient is caught in a self-stabilizing network of these vicious circles or dysregulations. A mechanical analogy to this interplay is a gear box in which moving a single gearwheel sets the whole gearing mechanism in motion.”

On the other hand, if the ME/CFS patient did not experience PEM, their body would instead be able to put its resources into healing the other dysfunctions in a more straightforward way. One theme I have noted in ME/CFS recovery stories, albeit anecdotally, is that the patient usually managed to avoid PEM for a very long time. Mitodicure could perhaps achieve the same effect, not in and of itself curing the illness, but rather making it much easier for the body to heal itself.

This is the case even though the pill is targeting a ‘downstream’ dysfunction in the illness. Calcium toxicity is a consequence of ME/CFS and not the cause. However, it is such an important consequence that, with it taken out of the picture, the body might just be able to do the rest of the job.

The action of Mitodicure is to improve the function of the cellular sodium-potassium pump. As a result, high intracellular sodium will cease, and— therefore— cellular calcium overload will also be avoided. Wirth expects the side effects to be mild. He is currently looking for an investor or consortium of investors to perform the necessary clinical trials and get Mitodicure to the market as the world’s first ME/CFS and Post-COVID ME/CFS pill. In the recent public Fatigatio conference in Germany, Wirth stated that around 21 million USD is the required investment.

Of course, medical research happens slowly and, even with funding, we will have years to wait for Mitodicure. But it is so important that this process is in motion. Not only could Mitodicure profoundly improve the lives of countless ME/CFS patients, but it could also single-handedly change political and mainstream medical perceptions of the illness. After all, if an ME/CFS-specific pill has a dramatic impact on the health of ME/CFS patients, then you cannot really maintain the psychosomatic argument anymore, can you?

I believe we are entering a time of greater hope for ME/CFS patients. As Wirth and Scheibenbogen write in their most recent paper:

ME/CFS is no more an enigmatic disease for which therapeutic concepts are missing. Since the assumed disturbances are functional in nature and are treatable by appropriate agents, there is a good chance of novel, highly efficacious drugs and even healing for this frequent and most debilitating disease. We appeal to politicians, pharmaceutical companies and stakeholders to support the rapid development of such promising new drugs.

Let us hope that their call is heard.

PS: Check out the recent interview of Prof. Wirth on Gez Medinger’s channel here.

About the Author:

Patrick Ussher has had ME/CFS for seven years. His newly published book, Understanding ME/CFS & Strategies for Healing, explains in an accessible way the breakthrough research of Prof. Carmen Scheibenbogen and Prof. Klaus Wirth (who wrote the book’s foreword). The book also discusses other research and treatments that Patrick has found helpful in his own journey.

In addition, he has a YouTube channel, Understanding ME-CFS, in which he talks about the research into ME/CFS and long COVID . In this video, for example, he talks about the Mitodicure pill.

He has written a medical hypothesis on the potential causes of excessive thirst in ME/CFS and long COVID and why this symptom has likely been historically misdiagnosed as ‘psychogenic water drinking.’ He also gives regular talks to patient groups such as The Irish ME Trust and has written for the ME/CFS blog, Health Rising, on various topics, including the thirst issue.

His website is www.patrickussher.com.