The role of epigenetic modification of BDNF and HDACs in pain and post-exertional malaise in ME/CFS

Principal investigators

Prof. Jo Nijs and Prof. Lode Godderis

Institutions

Vrije Univeristeit Brussel and the University of Leuven, Belgium

Start date

October 2020

Background and aim

Epigenetics is a fascinating field looking at genetic changes that can be passed from one generation to the next, not as a result of alterations in the DNA sequence, but instead caused by changes in gene activity and expression (how information from the gene is used to make proteins).

One consequence of epigenetics is the possibility that the behaviour and experiences of an individual can affect the health of their children and grandchildren, perhaps putting them at a higher risk of disease. Science fiction writers have also explored how epigenetics might allow knowledge and experience to be passed down multiple generations.

As far as we know, there are not yet any indications that the risk of developing ME/CFS can be inherited via epigenetics. However, there is evidence that epigenetic changes may play a role in the pathophysiology of the illness, including the post-exertional malaise experienced by many people with ME/CFS.

This is the area that Prof. Jo Nijs from Vrije Univeristeit Brussel, Prof. Lode Godderis from the University of Leuven and their colleagues are exploring in this research study awarded funding by ME Research UK.

These investigators’ previous research has uncovered the role of central sensitisation in the chronic pain experienced by many people with ME/CFS at rest and/or after exercise. This is the idea that the central nervous system is hypersensitive in these individuals, leading to an increased sensitivity to pain.

The mechanisms involved in central sensitisation are complicated, but two factors – and how they are altered by epigenetic changes – may be particularly important.

Brain-derived neurotrophic factor (BDNF) is a protein involved in a number of neurological functions. It is released during exercise and physical activity, but can also increase the sensitivity of pain pathways. In the researchers’ previous study funded by ME Research UK, people with ME/CFS had increased BDNF levels, but the methylation of DNA within the BDNF gene (an epigenetic mechanism) was lower than normal.

Histone de-acetylases (HDACs) are a group of enzymes known to be increased during neural sensitisation and pain, although their activity is decreased during exercise (in contrast to BDNF), and they have not yet been studied in ME/CFS.

This is some of the background of evidence behind this project being conducted by Profs Nijs and Godderis, in which they are investigating further the role of BDNF and HDACs in the central sensitisation and post-exertional malaise experienced by people with ME/ CFS, and the epigenetic changes occurring in these genes.

Eighty patients with ME/ CFS will be enrolled and split into two groups. The first group will undergo a session of aerobic exercise, while, as a control, the other will undergo a test designed to trigger emotional stress. Various clinical and laboratory assessments will be performed before and after these sessions, including measuring the expression of BDNF and HDACs in the blood, as well as DNA methylation in the BDNF gene and in the genes regulating HDAC expression.

Epigenetic changes have been shown to contribute to the pathogenesis of a number of disorders – including Alzheimer’s disease and some cancers – leading to the development of potential new treatments. The investigators hope that the same will be true in ME/CFS, and their results might ultimately lead to new diagnostic markers and treatment strategies.

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