What Leads to the Development of Multiple Sclerosis?


Research seeks to determine the genetic and environmental risk factors that trigger MS.

A recent study evaluated people at risk for developing multiple sclerosis (MS) to find what sequence of events leads to the development of the disease.

The research was done by investigators at Brigham and Women's Hospital and the National Institute of Neurological Disorders and Stroke (NINDS), who introduced the Genes and Environment in Multiple Sclerosis (GEMS) project published in the Annals of Neurology.

"This first report from the GEMS study is important because it shows that we can recruit the large number of family members that is necessary to perform a well-powered study of MS risk factors," said lead author Zongqi Xia, PhD.

When patients were enrolled in the study, they were given a web-based questionnaire with information that includes medical history, family history, and environmental exposures. They were also required to submit a sample of their saliva for DNA extraction.

"Since the disease likely starts many years before the first symptom appears, we do not yet understand how genetic and environmental risk factors come together to trigger MS," said co-senior author Daniel Reich, MD, PhD. "When a patient comes to see a neurologist for the first time, the process of brain inflammation is well underway, since many lesions have few or no symptoms."

The purpose of the study was to focus on the first-degree family members of MS patients, since they are 20 to 40 times more likely to develop the disease. However that risk is still relatively low, as it’s estimated that only 62 first-degree relatives out of 10,000 will be diagnosed over 5 years.

During the preliminary analysis, researchers tested a method to calculate the risk of developing MS. They identified a subset of family members with a higher risk of getting MS than the average family member.

Although this method cannot be used in a clinical trial yet, the risk score could help design long term studies for high risk patients, as well help predict who is at risk in order to get to it early.

"This report is an important first step,” said co-senior author Phil De Jager, MD, PhD. “We do not yet have a tool that we can use clinically to predict MS. To develop such tools further, and to develop a platform for testing strategies to prevent the disease altogether, we are expanding GEMS into a larger collaborative study that will accelerate the progress of discovery and bring together a community of investigators to overcome this important challenge.

“Overall, the risk of MS remains very small for most family members,” Jager said. “The most effective therapies for MS will ultimately be those that prevent its onset, as halting inflammation and disease progression are much more difficult once the disease has become established."

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