Mitodicure discloses its therapeutic concept and leaves stealth mode

The Cause of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Is an Acquired Disorder of the Mitochondria within the Skeletal Muscle

Twenty percent of all Long COVID patients go on to develop Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), something that is regarded as one of the worst possible consequences of Long COVID. The cardinal symptom of ME/CFS involves recurring and worsening exercise intolerance, even from the slightest exertion. Those who suffer from ME/CFS sometimes feel that their lives are nothing more than a vegetative existence. The disease often particularly affects young people, two thirds of whom are women. The start-up Mitodicure GmbH has worked out a therapeutic drug approach based on a working model on the pathophysiology of ME/CFS, to which it has contributed significantly and which has only recently been substantiated by clinical findings in patients.

The starting point of the working model is that, following certain viral infections, there then develops a particular kind of circulatory disorder. In some cases, this circulatory disorder can lead to a severe obstruction of capillary blood flow. As a result, the capillary blood flow then comes to a complete standstill, which leads, in turn, to an insufficient supply of oxygen (ischemia) into the muscles. As this standstill is temporary, blood perfusion will return, but this temporary reduction of capillary blood flow can reoccur regularly during exacerbations in the illness. In most Long COVID patients, this disorder in the blood capillaries will heal. In others, the constant interplay between ischemia and reperfusion will completely confuse the dynamic balance of various ion pumps within the membrane of the skeletal muscle cells. The result is an intracellular excess of calcium ions, something which then damages the mitochondria to finally cause ME/CFS.

This confusion of the ion currents stems, in large part, from a dysfunction of the Na+/K+-ATPase ion pump, i.e., the sodium-potassium pump. During muscle activation under healthy circumstances, this pump has to increase its turnover by a factor of 10 to 20. Normally, it primarily receives the command to do this via both adrenaline and the ß2 adrenergic receptors from within the cell membrane. However, this signaling pathway is disturbed in ME/CFS patients, partly because they carry autoantibodies against these receptors. Overall, this results in a vicious circle of far too little energy supply to the muscle tissue in ME/CFS patients, a situation that is then only worsened as each subsequent physical exertion will then further diminish the available pool of normally functioning mitochondria.

The aforementioned circulatory disorder creates a state of ‘global hypoperfusion’. The body of the ME/CFS patient will attempt to counter this state by releasing vasodilating tissue hormones in order to improve local blood flow into the skeletal muscles. However, it releases them in such abundance that they spill over from the tissue and into the bloodstream. These vasodilating tissue hormones can then reach every organ via the circulatory system and cause pain, cramps/spasms in internal organs and edema. This can explain why ME/CFS not only affects the muscles, but also can affect the brain, thereby creating, for example, its characteristic symptoms of brain fog and other forms of cognitive dysfunction. The aim of Mitodicure is to prevent this disorder of ion exchange during muscle activation and at the same time improve blood flow in the capillaries. Indeed, the company has a novel active ingredient that could be developed into a drug that corrects the defective ß2 adrenergic signaling pathway, thereby breaking simultaneously several key, underlying vicious circles of the illness. According to its founders’ plans, this compound could enter phase 1 clinical trials as soon as possible.