Identifying genes that cause a person to experience either an aggressive or mild form of MS has long been of interest in MS research, but has remained elusive – until now. A new study has now identified three changes within people’s genes that are linked to different disease courses in MS. This new genetic information may provide a way to predict outcomes early in the disease and help guide treatment decisions.
Genetic research in MS has identified more than 200 genetic changes that influence the risk of developing MS. Such research provides a wealth of information about the nature of MS even on a molecular level and reveals which biological pathways are involved in the disease.
However, genetic research has been less successful in identifying genes that influence disease course in MS. Research has shown that, in other diseases, genes often control disease course, dictating the ultimate severity of the disease. Obtaining this genetic information for MS would enable health professionals to predict the type of disease that a person will experience, which could in turn help to guide treatment choices. For example, if a person is predicted to have a more active disease, health professionals may choose a more aggressive therapy early in the disease course.
A new study, published in Journal of Neuroinflammation, may have found some elusive genes related to disease course in MS. In this study, researchers compared the genes of people with benign MS to those of people with aggressive MS. The individuals with benign MS had less disability (a score of three or lower on the EDSS or extended disability severity score) after 15 years or more and had never received any MS treatment. Those with the aggressive form of the disease had accumulated more disability (a score of 6 or more on the EDSS) in the first five years of MS, despite being treated for MS.
The researchers examined all of the genes in the genome, specifically in regions of the DNA that encode the instructions to make proteins. These parts of DNA have traditionally been thought to be more likely to play a role in disease progression. The study initially identified 16 genetic changes that differed depending on whether participants had benign or aggressive MS. The scientists then focused on three genes, called IGSF9B, NLRP9 and CPXM2. Changes in the first two genes were associated with benign MS, whilst changes in the last one was associated with aggressive forms of MS.
To help identify how these genes influenced the course of the disease, the scientists analysed the activity of each of the genes in different parts of the body, and found that, unlike some of the MS risk genes that are active in the immune system, these genes appeared to be active in brain tissue. The researchers suggest that the genetic changes may be affecting specific cell types within the brain, altering the course of disease in people with MS. These genes may also provide vital clues about which biological pathways are responsible for disease course in MS.
MS is an unpredictable disease and people with MS often say that this unpredictability is one of the hardest aspects of MS to deal with. Identifying genes related to MS, such as the ones found in this study, may eventually allow medical teams to predict outcomes in people with MS and tailor treatment and advice accordingly.
With thanks to MS Research Australia – the lead provider of research summaries on our website.