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In a major step toward discovering molecules that may be used as “markers” to predict MS disease activity and progression, researchers identified a pattern of gene expression (i.e., patterns of genes being turned on or off) within immune cells that was associated with quick conversion to MS in a study of 37 people with CIS (clinically isolated syndrome, a first event suggestive of MS). Senior author Sergio Baranzini, PhD, Jean-Cristophe Corvol, PhD and colleagues (University of California, San Francisco) report the results in an early online publication from Proceedings of the National Academy of Sciences of the USA (August 5, 2008). This study was funded by several sources including aCollaborative MS Research Center Awardto Jorge Oksenberg, PhD, from the National MS Society.
MS occurs when the immune system attacks the brain and spinal cord. MS is an unpredictable disease and its course varies among individuals. Previous research suggests that about one-third of patients who experience CIS, a single event denoting inflammatory damage to myelin in the brain or spinal cord, will “convert” to definite MS within one year, meaning that they will experience subsequent events and signs that make it possible to make a definite diagnosis of MS. That’s why identifying markers – such as patterns of genetic activity – in people at high risk for MS or in the earliest stages of the disease would be invaluable in assisting patients and clinicians to determine the best treatment options.
Dr. Baranzini’s team obtained blood cells from 37 people with CIS and 29 healthy controls without CIS. Using microarrays (technology in which robotic machines arrange thousands of gene sequences on a single microscope slide), they analyzed the gene expression patterns – the levels of gene function that were instructing these cells’ activities – at the time of CIS diagnosis and after one year. The team followed the patients with clinical examinations and MRI scans for 30 months, to determine who converted to clinically definite MS.
The researchers found that 108 genes were significantly different in their level of activity in a subgroup of people who developed MS within nine months. One gene in particular was less active – TOB1. This gene functions within the immune system to regulate T cells, limiting their proliferation. In MS, these cells are thought to be the major players in the attack on the brain and spinal cord.
“This study is truly exciting – it’s a step toward making MS predictable and preventable,” says John R. Richert, MD, Executive Vice President of Research & Clinical Programs. “This is precisely the kind of progress we were hoping for when we funded their research center to focus on these types of markers. We look forward to learning more about this gene activity and how it will eventually be translated into diagnostic or treatment strategies for people with MS.”
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