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New gene identified in multiple sclerosis disease activity.

A new study led by investigators at Brigham and Women’s Hospital (BWH) reports the discovery of a genetic variant that is associated with a patient’s likelihood of responding to interferon-beta, one of the medications used in treating multiple sclerosis (MS). Published in the Annals of Neurology, the new study also presents evidence that the affected gene, SLC9A9, may have a broader role in regulating the development and activity of certain immune cells that play important roles in inflammatory diseases like MS.

The team state that a proportion of MS patients experience disease activity despite treatment. The early identification of the most effective drug for a given individual is critical to impact long-term outcome and to move toward a precise treatment approach.

To find predictive indicators of a patient’s response to treatment, the team, which included researchers from the Ospedale San Raffaele performed a genome-wide association study (GWAS) in MS patients from Brigham and Women’s Hospital, San Raffaele Hospital and seven academic MS centers in France, all of whom were being treated with the drug interferon-beta. The variant most predictive of whether or not a patient would respond to the drug was found in the gene SLC9A9.

The current study highlights the fact that genetic variation has a role in the course of a patient’s disease in MS, but that this role is modest and will require much larger studies to be understood in detail, state the team.  Discovered in Italian patients, the observation was replicated in other Italian patients as well as patients in Boston and patients in France.

The researchers now plan further work to validate the results in other collections of patients, particularly patients treated with other MS medications, to evaluate whether the effect of the genetic variant is limited to interferon beta treatment or is relevant to other clinical MS treatments.

The variant detected has a confirmed but weak role in MS. However, laboratory work in this report shows that the loss of the SLC9A9 gene leads immune cells to become much more likely to provoke damaging immune reactions.

The team conclude that manipulations of this gene in mice and in human cells will lead to better understanding of the mechanisms that are involved in the autoimmune response that causes MS.

Source:  Brigham and Women’s Hospital (BWH)

Study implicates new gene in multiple sclerosis disease activity - neuroinnovations

 

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