June 25, 2014
MS Society-supported study reports biological differences that can help identify people with aggressive MS disease
Approximately 80% of people with multiple sclerosis present with a relapsing-remitting course. In this type of MS, relapses, which can also be called ‘flare-ups’ or ‘attacks’, are separated by periods of recovery during which symptoms do not appear.
Much work in the field of MS has been dedicated to understanding what happens in the body during a relapse, which is thought to be driven by immune cells that enter the central nervous system (CNS) and cause inflammatory damage to white matter. This research has resulted in the development of therapies which are capable of managing MS symptoms by controlling immune cells and reducing inflammation.
Unfortunately, improvements in treatment have not been seen for the debilitating form of MS known as progressive MS. This type of MS is, as the name suggests, is characterized by advanced neurological damage resulting in more pronounced symptoms and disability. Researchers are addressing the progressive MS treatment gap by gathering as much information about this type of MS as possible. They are also working to develop the appropriate tools to that could help clinicians identify individuals who are at high risk of converting to progressive MS, and treat them as early and effectively as possible.
One MS Society supported study led by McGill University researcher Dr. David Haegert has discovered a number of unique biological indicators in a population of people with rapidly progressing MS. This work uncovers important clues about the biological differences underlying the different types of MS, and can potentially lead to the creation of screening technologies that can identify people with advanced disease.
Dr. Haegert and collaborators, including MS Society funded scientists Drs. Jack Antel and Amit Bar-Or, examined several immune-system related genes in people with progressive MS and healthy individuals (controls). They looked specifically at genes associated with the T cell, a type white blood cell involved in MS. They did this by collecting blood samples from the study participants and isolating the T cells to look more closely at their DNA, which houses the genes of interest. The overall aims of the study were to find a link between T cells and progressive MS, and look for any genetic patterns in T cells associated with rapidly progressing disease.
What they found:
The study reported significant differences in T cell genes in people with progressive MS compared to healthy individuals. Interestingly, researchers also discovered notable genetic differences between people who transitioned to progressive MS sooner versus later. The TOB1 gene, for example was found to be turned off in people with more rapidly advancing progressive MS. This observation supports data from a recent study, which showed that low levels of TOB1 is linked with high risk for conversion to MS in people displaying early signs of the disease. Dr. Haegert identified a number of other T cell related genes which were turned on in the rapidly progressing MS group versus the group whose MS progressed more slowly. He proposed that the group who converted to progressive MS more quickly may be experiencing a more active/aggressive progressive MS disease course.
This work funded by the MS Society adds to the growing body of evidence which supports the idea that MS is a result of an imbalance in the immune system. This means that there is an abundance of harmful ‘self-reactive’ T cells, and not enough ‘regulatory’ T cells which are the good guys that control levels of inflammation. By observing differences in T cell genes, researchers were able to divide the progressive MS group into different categories based on disease severity. Those individuals who moved from relapsing-remitting to progressive MS more quickly (about 12 years from diagnosis) showed high levels of specific T cell genes associated with more inflammation, compared with people who developed progressive MS much later (about 25 years after diagnosis). This study provides critical information about the biological differences in people who experience difference courses of MS, and can potentially identify people with MS who will convert to progressive MS more quickly.
Zastepa E et al. Naive CD4 T-cell activation identifies MS patients having rapid transition to progressive MS. Neurology 2013 Jan 24 [Epub ahead of print].