Unlocking the Mystery of Fatigue: Acetylcholine Therapy for Post-COVID-19 Syndrome

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Unlocking the Mystery of Fatigue: Acetylcholine Therapy for Post-COVID-19 Syndrome

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Unlocking the Mystery of Fatigue: Acetylcholine Therapy for Post-COVID-19 Syndrome

So far, fatigue has been explained as being of two types: “physiological fatigue” and “pathological fatigue.”

“Pathological fatigue” seen in conditions like chronic fatigue syndrome, depression, and post-COVID-19 syndrome is different from the kind of fatigue where resting for a day leads to recovery. Many patients suffer from this, emphasizing the urgent need for new drugs.

The difference between “pathological fatigue” and “physiological fatigue” lies in whether there is inflammation in the brain. Why does “pathological fatigue,” such as in post-COVID-19 syndrome, result in brain inflammation?

Through experiments on mice, we discovered that there is a deficiency of the neurotransmitter “acetylcholine” in the brain. Increasing acetylcholine suppressed brain inflammation and eliminated feelings of fatigue and depression. The cause of brain inflammation was found to be a lack of acetylcholine.

Acetylcholine has anti-inflammatory effects. Put simply, a deficiency of acetylcholine is like having a fire in the brain with the brain’s “fire extinguisher” malfunctioning.

This suggests that supplementing acetylcholine could lead to recovery from “pathological fatigue.” In fact, the drug “donepezil” (brand name Aricept), used to alleviate acetylcholine deficiency in the brain in mouse experiments, is already used as a treatment for dementia.

Based on these findings, it is hoped that administering donepezil to patients experiencing fatigue after COVID-19 infection at an early stage could prevent post-COVID-19 syndrome. Even in cases where post-COVID-19 syndrome has already occurred, early treatment may be effective.

Regarding donepezil, a “Phase 2 trial of donepezil for post-COVID-19 syndrome” funded by public research grants is scheduled for the fiscal years 2022-23. If this trial is successful, a treatment for post-COVID-19 syndrome will become available. Furthermore, the use of donepezil as an antidepressant may also become clearer.

Until now, the mechanism of brain inflammation has focused solely on the role of “accelerators” that increase inflammation. Drug development has also been focused on how to reduce these accelerators. However, in reality, it was necessary to pay attention to the “brakes” that stop inflammation.

In the future, if we can find the cause of the brake failure or develop drugs that enhance the brakes, we may be able to solve many diseases related to fatigue from their root causes.

Unlocking the Mystery of Fatigue: Acetylcholine Therapy for Post-COVID-19 Syndrome

(source:internet, reference only)

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