Dr Audrey Brown
Institute of Cellular Medicine, Newcastle University, Newcastle, UK
Abnormal muscle fatigue is one of the most common symptoms reported by people with ME/CFS, and can occur even after periods of only mild exercise.
Since 2006, ME Research UK has provided pilot funding for a number of projects at Newcastle University exploring the mechanisms underlying this symptom, and one of their findings was of a higher than normal build-up in acidity during exercise, and a slower recovery back to resting levels afterwards. This suggests abnormalities in the way muscle cells handle acid in ME/CFS.
Following this, Prof. David Jones and Prof. Julia Newton went on to look more closely at the function of muscle cells. To achieve this, they took muscle cell biopsies from ME/CFS patients, and cultured them to provide sufficient numbers of cells to examine in standardised laboratory conditions without the influence of other complicating factors.
A series of electrical pulses was applied to these cultured muscle cells to simulate the muscle contraction that occurs during exercise, and the researchers found two defects in their function.
Activation of AMP-activated protein kinase (AMPK) and glucose uptake were both impaired; AMPK has an important role in regulating energy in the cell and is normally activated during muscle contraction, while glucose is an important energy source.
Although AMPK was not activated by simulated muscle contraction in these cells from ME/CFS patients, later experiments showed that it could be activated by treatment with metformin, a drug known to have this effect in healthy cells. This raises the possibility of whether a treatment such as this could improve muscle function in patients.
Following on from these fascinating results, ME Research UK has awarded further funding for Dr Audrey Brown and Prof. Newton to continue investigating these abnormalities in AMPK activation.
Their new project will use specific AMPK activators (used in the treatment of other diseases such as diabetes) to explore the mechanism through which AMPK is activated pharmacologically, but is not activated by muscle contraction. The researchers will also examine the function of the mitochondria (the powerhouses of the cell) in ME/CFS patients and healthy control subjects.
These results may help to determine whether pharmacological activation of AMPK could improve muscle function in ME/CFS, and could help identify potential new targets for treatment.