Simon McGrath is the author of the ME/CFS Research Review blog.
The hallmark symptom of ME/CFS is post-exertional malaise (PEM), a prolonged, grim and disproportionate response to exertion. While Dr W. Ian Lipkin’s NIH-funded Collaborative – the Center for Solutions for ME/CFS – is focusing primarily on how problems in patients’ gut microbiomes might drive the disease, his team is also probing deeply what happens when patients exert themselves.​ Lipkin says that the exertion studies are so important that the Collaborative will devote a third of its research resources to it.
When I spoke to Lipkin about the Collaborative’s work, he also said he was very hopeful that there would be real progress for patients within five years. More on this later in the blog.

Exertion studies

The Collaborative has a simple idea for exploring PEM: use two different exertion tests that should provoke symptoms in patients and then see what happens, both to how patients feel and to their biology.
If biological changes, such as those to cytokines, ramp up along with symptoms then it’s more likely that the biological changes are directly related to the illness and should give clues as to their role. Any insights into the nature of PEM could lead to a much better understanding of ME/CFS.
Fifty patients and controls will undergo a single maximal exercise test, a sure-fire way to provoke PEM. Patients’ symptoms will be measured before the test and then 24 hours, 48 hours and one week after the test. Crucially, researchers will collect blood, saliva and stool (poop) samples on two occasions: before the test, and 24 hours later.
The other, gentler exertion test, called LEAN, simply involves patients leaning against a wall for ten minutes. This test is designed to induce orthostatic intolerance – the development of symptoms when standing upright that ease when lying down – which is a common problem in ME/CFS.
Symptoms (including brain fog, tested using a special phone app) will be measured just before the test and at three time-points afterward. Researchers will also check blood pressure and take other clinical measures both before and immediately after the test.
The researchers running the Collaborative’s immune study will apply transcriptomics (which examines gene expression) and metabolomics to blood samples from both the exertion tests. And this should reveal any biological changes as symptoms kick off.
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