UK launches trial of drug to tackle fatigue in long Covid patients

In the UK, the first clinical trial of a drug that targets fatigue and weakness in people with long Covid was launched. This is the first time that a drug has been tested in long Covid patients, who were not admitted to hospital during their initial infection.
AXA1125 is a drug that targets mitochondria, cellular power plants. It is believed to be defective in a subset of Covid patients suffering from severe fatigue. If successful, it could pave the way for similar trials in patients with other forms of post-viral fatigue, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Mitochondria regulate cellular processes and are responsible for transforming chemical energy from our diets to adenosine Triphosphate (ATP), the energy currency cells rely on to drive vital reactions.

ATP is quickly depleted so cells need to constantly replenish it. Glycolysis is a process that produces lactic acid, which can be used to make ATP. However, ATP can be produced more efficiently by oxidative phosphorylation which involves mitochondria.

Evidence is mounting that Sars-CoV-2 can hijack cells' mitochondrial, causing viral replication to increase and disrupt ATP production.

It acts as a fuel switch. The virus infects the mitochondria and attempts to make more viruses by moving it towards glycolysis. However, it damages the cells, according to Bill Hinshaw, president and chief executive officer of Axcella.

Long-term Covid patients are estimated to suffer from fatigue, with 56% also struggling to exercise. These symptoms were initially thought to be due to organ inflammation. Dr Betty Raman, a University of Oxford researcher, is currently studying the effects of Covid-19 on organ function. Six months later, however, we discovered that while the heart and lungs had been able to recover, the people who were still suffering from the symptoms were unable to exercise.

Further investigations revealed that the patients were accumulating more lactic acid than normal, which could be indicative of mitochondrial dysfunction. Raman stated that a healthy, normal person's mitochondria would be active in replenishing ATP for energy.

AXA1125 can normalise mitochondrial metabolism in conditions where it is out of balance. It has shown promising results in non-alcoholic liver disease patients.

Raman will be conducting a study on 40 patients suffering from severe post-Covid fatigue. The purpose of the study is to determine if AXA1125 can increase exercise tolerance, reduce fatigue, and improve mitochondrial metabolism in muscle tissue. This can be visualized using imaging techniques. Half of the patients will receive AXA1125 over 28 days and half will be administered a placebo drug. The results are expected to be available by mid-2022.

Raman stated that although I don't believe this drug will cure all the long Covid, it could help a large number of patients.

Professor Amitava Banerjee of University College London is leading a separate trial for long Covid diagnostics. She said that it is great to test different drugs and different mechanisms. Although we have known about mitochondrial dysfunction in fatigue for some time and it has been studied extensively, we don't know how common it is among this patient population or how it correlates to the severity of their symptoms.

The approval is pending to start trials of repurposed medications such as aspirin and antihistamines in Covid long-term patients who were not admitted. Already underway is a trial to find treatments that can boost recovery for Covid-19 patients who are discharged from the hospital.

Banerjee stated that no matter what we were trying, we know that there are tens to thousands of people waiting to be seen. Any new treatments must be easily translatable.

According to Dr Charles Shepherd (a medical advisor at the ME Association), AXA1125 may be able to reduce fatigue in long Covid. This could have important implications for ME/CFS patients. There is a lot of evidence that mitochondrial dysfunction can be present in ME/CFS. This may also play a role in muscle energy metabolism and activity-induced fatigue.