A genetic mechanism has been spotlighted in a recent study as the likely culprit that may cause some patients with multiple sclerosis (MS) to progress more quickly than others to a debilitating stage of the disease. According to researchers at the University of San Francisco (UCSF), the absence of the gene Tob1 in CD4+ T cells played a key role in the onset of more serious disease in an animal model of MS.
Sergio Baranzini, PhD, UCSF, (pictured right) notes that developing a test for the gene could potentially predict the course of MS in individual patients. In the study, researchers Baranzini, Scott Zamvill, MD, and Jorge Okensberg, PhD, report that they targeted two goals. These goals centered on recapitulating in an animal model what researchers had observed in humans, and uncovering the potential mechanism by which it occurs.
The researchers report that during the study, they observed that when an MS-like disease was induced in mice genetically engineered to be deficient in Tob1, the mice exhibited significantly earlier onset when compared with wild-type mice, and also developed a more aggressive form of the disease. A recent news release also indicated that subsequent experiments revealed that the absence of Tob1 in just CD4+ T cells was a key factor. Researchers reportedly sough to demonstrate this by transferring T cells lacking the Tob1 gene into mice that had no immune systems but had normal Tob1 in all other cells. The results suggest that mice developing earlier and more severe disease than mice that had normal Tob1 expression in all cells including CD4+.
Baranzini states that the results show, “Tob1 only needs to be absent in this one type of immune cell in order to reproduce our initial observations in mice lacking Tob1 in all of their cells.”
According to the study, the researchers also found the likely mechanism of disease progression in the Tob1-deficient mice to be higher levels of Th1 and Th17 cells.
Baranzini designates the research as significant for humans, because the presence of absence of Tob1 in CD4+ cells could eventually serve as prognostic biomarkers that could assist clinicians in predicting the course and severity of MS in individual patients.
Photo Credit: UCSF