A hypothesis by Wirth and Scheibenbogen suggests that ME/CFS is caused by impaired ion exchange processes in muscle cells, leading to mitochondrial damage. This creates a vicious cycle in which mitochondria are further damaged, explaining the symptoms of ME/CFS as well as Post-Exertional Malaise (PEM).
1️⃣ Circulatory disorders and ion exchange
- Infections can damage the endothelial cells that line the inside of blood vessels, impairing blood flow through the capillaries.
- This leads to a lack of oxygen in the muscles and organs.
2️⃣ Reaction to stress
- During physical activity, the muscles require more oxygen and nutrients, but due to impaired blood circulation, this need cannot be met.
- The body reacts by increasing the heart rate, which further lowers the blood pressure in the capillaries.
3️⃣ Disturbance of the sodium-calcium exchanger (NCX)
- Normally, NCX transports calcium out of muscle cells and sodium into them.
- In ME/CFS, impaired blood circulation and lack of oxygen lead to an increase in sodium levels in the cells.
- If the sodium content exceeds a certain threshold, the NCX reverses its function and pumps calcium into the cells instead of transporting it out.
4️⃣ Follow
- The excessive accumulation of calcium in muscle cells damages the mitochondria, which are responsible for energy production in the cells.
- Damaged mitochondria release aggressive oxygen radicals, which further reduce ATP levels (important for cellular energy) and additionally inhibit sodium-potassium ATPase (an ion pump).
5️⃣ PEM and the vicious circle
- If the stress is renewed, the already weakened mitochondria suffer further damage.
- This gradually leads to a reduction in the number of functional mitochondria.
- When intracellular sodium reaches a critical level, the NCX switches and causes cells to become overloaded with calcium again.
- This leads to a significant worsening of symptoms (PEM).
- The health condition continuously deteriorates due to this endless cycle.
Mitodicure plans to start the Phase 1 trial for its ME/CFS drug candidate in fall 2025, subject to investor search and securing financing.
Source of the article: riffreporter, Claudia Schreiner