Resetting ME/CFS with epigenetics? Part 2

As we continue to look at epigenetics and how it might be relevant in ME/CFS, here is part 2 of Cort Johnson’s article on this area in which he talks about some of the research funded by ME Research UK. Read part 1 here. Cort writes the excellent Health Rising blog on ME/CFS research news.

Last week, we introduced the fascinating world of epigenetics, and explored some of the first research suggesting how it might have a role in ME/CFS. But how is ME Research UK helping to further this area?

Just last year, new ground was broken by an ME Research UK-funded epigenetics study conducted by Prof. Jo Nijs and colleagues at Vrije Universiteit Brussel in Belgium. The latest in a programme of research on this topic, the study found increased levels of brain-derived neurotropic factor (BDNF) in people with ME/CFS. BDNF has been linked with pain in fibromyalgia several times, but it is also particularly interesting in diseases such as ME because BDNF levels are elevated by ME’s own brand of kryptonite: exercise.

Those increased BDNF levels in patients were associated with increased symptoms at rest. However, the real twist was the finding of low levels of DNA methylation (an epigenetic modification). That led the authors – piggybacking on findings from another study – to suggest that an infectious event had altered BDNF’s epigenetics, causing BDNF to become overly activated during exercise in ME/CFS. High levels of BDNF may then be sensitising pain pathways, leading to post-exertional malaise (PEM).

That promising result set up a new study, recently funded by ME Research UK, and led by Prof. Nijs as well as Prof. Lode Godderis from the University of Leuven, looking at the role of epigenetic modification of BDNF in pain and PEM in ME/CFS.

First, the study will assess a most interesting question: could exercise be sending BDNF levels into the stratosphere in ME/CFS? If it is, then a direct link between exercise and the pain it causes in the disease may have been found. If low BDNF methylation rates are again found, the study may also point to a potentially modifiable reason for the high BDNF levels. 

The study will also examine another exercise-triggered factor – enzymes called histone de-acetylases (HDACs) that usually decline during exercise, but have never previously been studied in ME/CFS. They are also associated with increased pain.

We don’t yet fully understand what role epigenetics plays in ME/CFS, but the findings so far – increased levels of epigenetic changes in metabolic, immune and nerve factors – make perfect sense given what we know about the illness.

Plus, this new epigenetics study from Belgium is aimed right at very heart of ME/CFS: exercise. The factors involved – an infection-triggered epigenetic change possibly associated with exercise and pain – all add up very enticingly.

Time will tell, of course. All we can do is look, but this effort has the potential to provide something rare: a specific epigenetic target linked to PEM, which could potentially be used to reset at least part of ME/CFS.

In the meantime, yet another ME Research UK-funded study looking at a different aspect of epigenetics in ME/CFS has just started in Spain, and we will introduce that next week.

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