ME Research UK’s first Founders’ Science Writing Award was won by Hollie Watmuff. Formerly a postdoctoral research associate at New York University, Hollie is now an Associate Medical Writer. Here is her winning entry on using non-coding RNA to diagnose ME/CFS.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an incurable, debilitating illness that is characterised by joint and muscle pain, brain fog, and extreme exhaustion followed by no improvement in symptoms after rest.
As symptoms are so broad, they often go unrecognised as ME/CFS by medical professionals who aren’t familiar with the illness. Instead, patients can be misdiagnosed with a condition that presents in a similar way – such as depression or another chronic disease (an example being fibromyalgia). Ultimately, this can lead to unsuitable treatment and long wait times for a proper ME/CFS diagnosis.
DecodeME
The DecodeME study, the first of its kind, aims to address this issue by zooming in on the changes to the genetic code (DNA) of people with ME/CFS. By analysing the DNA present in saliva samples, researchers aim to identify significant differences between people with ME/CFS and healthy controls. In the future, these results could be used to diagnose ME/CFS through genetic testing.
Another exciting outcome from the DecodeME study is that it will aid in understanding the biological causes of ME/CFS. DNA contains all the instructions that our bodies need to function properly – providing the blueprint for all the major systems of the body, including the immune, nervous and gastrointestinal systems. Any changes to a region of DNA that can be directly linked to a system that is abnormally regulated in ME/CFS could be highlighted for further study. With this in mind, an area of biology that is directly related to our DNA and has the potential to play a key role in the future of ME/CFS research is non-coding RNA.
What is non-coding RNA?
Prior to the 21st century, most processes in the body were thought to be carried out by molecules called proteins. The roadmap to produce proteins begins with DNA, whereby DNA is used as a template to make another molecule called RNA, which is then used as a template to make protein.
The body uses RNA as an intermediate step to allow for a quick response to changing bodily needs by rapidly destroying and removing the RNA – the body can’t remove its DNA, otherwise it could never produce protein again! Therefore, the main role of this RNA “middleman” was thought to revolve around its ability to make protein. However, in the past 20 or so years, non-coding RNA molecules have gained huge traction as an exciting new area of research.
Non-coding RNAs come in all different shapes and sizes, but their common feature is that they don’t make proteins. Instead, they have a wide variety of alternative tasks that are vital for proper functioning of the body. In relation to ME/CFS, current research shows that non-coding RNAs have functions within the immune response, the nervous system and metabolism – systems which are thought to be abnormally regulated in ME/CFS, potentially tying non-coding RNAs to the disease.
Using non-coding RNAs to diagnose ME/CFS
The link between non-coding RNA and ME/CFS is already beginning to be uncovered. In 2023, researchers collected blood samples from 40 ME/CFS patients and tested them for a difference in the types and amounts of a certain type of non-coding RNA: microRNA. Compared to healthy controls, they found a higher presence of three microRNAs and, interestingly, were able to link the amount of the microRNAs to the severity of ME/CFS.
A slightly older study, published in 2018, examined another class of non-coding RNA: long non-coding RNA. They chose to study 10 long non-coding RNAs tied to the function of the immune system, metabolism, nervous system and the body’s response to stress – bodily functions that are thought to be abnormally regulated in ME/CFS patients.
From 44 blood samples, they found that three long non-coding RNAs were present in higher amounts and, similarly to the previous study, two of these three could be linked to ME/CFS severity. The two long non-coding RNAs linked to disease severity were: NTT, a long non-coding RNA involved in the immune response, and EmX2OS, which is involved in the nervous system.
These two studies show that non-coding RNAs could be used to diagnose and gauge the severity of ME/CFS. However, a limitation is the small number of ME/CFS patients tested. To draw more concrete conclusions, a larger number of patients should be tested for non-coding RNA differences. This is one area where the DecodeME study will excel, as they are aiming to test the DNA of at least 20,000 people.
Does the future lie with non-coding RNAs?
The broad biological importance of non-coding RNA has only been uncovered in the past 20 or so years, making this a fast-growing and fascinating area of research. Additionally, due to the connection between DNA and non-coding RNA, the results of the pioneering DecodeME study may unlock further links between ME/CFS and non-coding RNAs.
As research into non-coding RNA and our understanding of ME/CFS evolve side-by-side, the scope for finding a non-coding RNA that could be used as a vitally needed diagnostic factor, or could be targeted for the treatment of ME/CFS, provides an exciting direction for the future of ME/CFS research.
You will be able to read the second-placed entry by Krista Clarke, from the University of Surrey, next week.
