Researchers Explore a Possible Biomarker That May Help Predict MS Disease Progression
June 27, 2013
Having a simple test to reliably predict the course and progression of multiple sclerosis would greatly inform treatment decisions, but so far such a test or other biological indicator, or biomarker, hasn’t been verified for MS. A step in that direction was recently taken by California researchers, in a study co-funded by the National MS Society, examining a molecule called Tob1. Previously they found that when Tob1 is abnormally low in certain blood cells, it leads to a high risk of disease progression, and in this study in mice, they found additional evidence for its role in disease activity. Additional research may lead to the use of this molecule as a predictor of who is at risk for MS progression. Drs. Sergio Baranzini, Schulze-Topphoff and colleagues at the University of California, San Francisco and Stanford University report their findings in the June 24, 2013 issue of the Journal of Experimental Medicine.
Background: Predicting MS onset, disease progression, and response to therapy are critically important for making treatment decisions and improving quality of life for individuals who have MS. Having biomarkers whose presence or absence can serve as an indicator of a particular change in disease is of utmost importance for predicting such changes in MS and for conducting better clinical trials. Reliable predictive biomarkers are not yet available in MS.
Immune cells called CD4+ T cells can make MS worse. In a previous study by the same team, low levels of a molecule called “Tob1,” which is seen in CD4+ T cells, were associated with progression from the first clinical attack (known as “clinically isolated syndrome” or “CIS”) to clinically definite MS. They reported that 92% of people who had CIS and who also had significantly reduced levels of Tob1 progressed to clinically definite MS within 9 months. In contrast, only 20% of people with normal levels of Tob1 progressed to MS after experiencing the first clinical attack. Thus, low Tob1 may serve as a biomarker for progression from CIS to MS. For the current study, the team further explored the significance of Tob1 by studying a mouse model of MS called EAE.
The study: Through a series of studies, the team found that mice that were genetically engineered to be missing Tob1 in their CD4+ T cells had an earlier onset of EAE, and their disease was more severe, and lasted longer than in mice with normal levels of Tob1. In addition, harmful CD4+ T cells that increase inflammation were present at higher levels, and there were fewer of the regulatory type of immune cells that can dampen inflammation. The researchers concluded that Tob1 appears to directly affect the CD4+T cells that play a large role in EAE and in risk of MS.
Comment: This study offers new evidence that a molecule, called Tob1, associated with immune cells has potential as a promising biomarker that could indicate people who are likely to progress to full-blown MS after a first attack. The study also opens up possibilities for new therapeutic interventions in which increasing Tob1 could possibly prevent full-blown MS after an initial attack, or reduce disease activity in people who already have MS. Additional research is needed to verify and expand these findings.