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Researcher
Prof. Jo Nijs
PhD student
Jente Van Campenhout
Institution
Vrije Universiteit Brussel, Belgium
Start date
October 2023
Funding
ME Research UK with the financial support of the Fred and Joan Davies Bequest
Background
The mitochondria are often called the power plants of the body. These structures are found in every cell in the body, and their role is to convert energy from our food into a form our cells can use.
It therefore seems logical that abnormalities in the mitochondria might play a role in ME/CFS, an illness that is characterised partly by an apparent lack of energy. Considerable research has addressed this question, but many of the findings have been conflicting. This could be because people with ME/CFS present with a wide range of symptoms.
The idea behind this PhD project from Prof. Jo Nijs, Dr Andrea Polli, Dr Jolien Hendrix and the team at Vrije Universiteit Brussel is that mitochondrial function in people with ME/CFS may be linked to the activity of their autonomic nervous system. And the PhD student carrying out this work is Jente Van Campenhout.
The autonomic nervous system controls involuntary processes in the body such as heart rate, circulation, etc. There is extensive evidence of autonomic abnormalities in ME/CFS – including orthostatic intolerance on standing, heart rate variability, and gastrointestinal symptoms – and it is possible to divide patients into autonomic subgroups (or phenotypes) according to how severely they are affected.
Associations between mitochondrial dysfunction and specific autonomic symptoms raises the question of whether mitochondrial dysfunction in ME/CFS depends on which autonomic phenotype an individual belongs to. And the researchers suggest that this link may be related to the expression of an enzyme called mitochondrial DNA methyltransferase.
Objectives
This is the question that Jente will be exploring in her PhD project. Over the course of two visits, she will assess a number of autonomic, clinical and biological measures in 75 people with ME/CFS and 15 healthy control subjects, before and after two procedures.
The first procedure is a bout of submaximal exercise on an exercise bike, in order to create a high-energy demand situation and stress the mitochondria. The second is an active standing test designed to stress the autonomic nervous system.
The data collected during these assessments will include measures of autonomic nervous system activity, mitochondrial dysfunction, and signs of mitochondrial DNA methyltransferase activity. Jente and the team will also assess the presence and severity of post-exertional malaise at 1 and 7 days after these procedures. She will then subgroup patients according to their autonomic phenotype, and analyse differences in mitochondrial dysfunction between these subgroups.
Potential benefits
Accurately subgrouping patients in this way could help to improve the diagnosis of people with ME/CFS, as well as determining their prognosis, and guiding the selection of appropriate therapies. While this may have immediate advantages for research, the use of subgroups in a clinical setting would need additional work to assess its validity and reliability.
Jente explains more about her project in this video.
