A simple blood test identifies epigenetic changes in people with MS and tracks their responses to an MS medication.
Research undertaken over many years has led to a number of gene discoveries with over 200 genetic changes identified with respect to the risk of developing MS. To better understand the role of genes in MS, researchers are now setting their sights on a related field that focuses on gene regulation. The field of epigenetics refers to the study of a variety of factors that influence the way DNA code is read by cells, without changing the actual DNA sequence. Epigenetic factors turn genes on and off within different cell types and they can be influenced by environmental factors – providing a link at the molecular level between genes and the environment.
The team at the Hunter Medical Research Institute, led by Professor Jeannette Lechner- Scott, are interested in the way genes are regulated in MS. They have completed several studies looking at different epigenetic factors in MS.
The first study examined changes to epigenetic markers in red blood cells in MS, with the hope that they might be able to uncover some new biomarkers for use in diagnosing and monitoring MS.
Awarded an MS Research Australia incubator grant in 2017, Professor Lechner-Scott and her team investigated microRNA levels in red blood cells in people with relapsing remitting MS and people without MS. MicroRNAs are short molecules of DNA-like material that are known to play a role in the activity of genes. The researchers found that microRNAs do differ in people with MS in comparison to people without MS. Published in the medical journal BMC Medical Genomics the study identified three microRNAs that were altered in MS. One of the microRNAs, in particular, was shown to be linked with the recent results of cognitive function tests (thinking and memory) in the people with MS. In addition, when the levels of the three microRNAs were combined they provided a “signature” that could distinguish people with relapsing remitting MS from people without MS.
The second study was interested in whether DNA methylation, another type of epigenetic marker, is associated with the risk of developing MS and whether they are associated with disease progression, that is, the conversion from relapsing remitting MS to secondary progressive MS. DNA methylation occurs when molecular tags known as “methyl groups” are added to the DNA at specific locations and these tags are able to change the activity of the underlying genes.
Funded through an MS Research Australia project grant with funding support from the MS Angels and MS WA, the study published in the journal Multiple Sclerosis Journal – Experimental, Translational and Clinical. The study focussed on the role of DNA methylation specifically in people with relapsing remitting MS who were being treated with the MS medication dimethyl fumarate. Since methylation changes in different cell types, they looked at a specific type of immune cell from the blood known as a CD4 T cell and compared the methylation levels before and after treatment with dimethyl fumarate. This is the first time that methylation levels have been investigated over time with respect to this treatment.
They found 945 areas overall that showed differences in methylation, and of these, almost all showed higher levels of methylation after the treatment. Four of the genes were singled out as particularly important since they were affected by multiple methylation changes in regions associated with the regulation of gene activity. This may provide evidence for exactly how dimethyl fumarate is working in MS.
Epigenetic markers in the blood, either microRNAs or DNA methylation, are of immense interest since they may provide a way to track changes in an individual’s disease or response to treatment through a simple blood test. Biomarkers may also be useful as an outcome or tracking measure in clinical trials. These types of biomarkers are urgently needed to help shorten the length of clinical trials and speed up results from clinical studies. Changes to gene regulation will also give us clues about the mechanisms underlying MS and provide new targets for developing therapies.