A research team at Brigham and Women’s Hospital (BWH) in Boston and the National Institute of Neurological Disorders and Stroke (NINDS) launched a study on people at risk for developing multiple sclerosis (MS), a debilitating disease that affects more than 400,000 people in the United States and about 2.5 million people worldwide.
The study focuses on first-degree family members of patients — children, siblings, parents — with MS, with the aim to understand the sequence of events beneath the development of the condition. The study is also seeking to develop and test early interventions for people at risk for MS.
The Genes and Environment in Multiple Sclerosis (GEMS) project was recently published in the Annals of Neurology in an article titled “Genes and Environment in Multiple Sclerosis Project: A Platform to Investigate Multiple Sclerosis Risk.”
“Early detection of MS means the possibility of earlier treatment, which could delay the accumulation of disability,” explained the study’s co-senior author, Dr. Phil De Jager, director of the Program in Translational NeuroPsychiatric Genomics at the Ann Romney Center for Neurologic Diseases at BWH, in a press release. “Our long-term goal is to map out the sequence of events leading from health to disease, in order to be able to identify and intervene early in individuals at high-risk of MS.”
The GEMS project establishes a platform to investigate the events leading to MS in at-risk individuals. In its first four years, the study recruited 2,632 subjects from every state in the U.S. The study aims to enroll 5,000 first-degree relatives; the study will continue for 20 years.
“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 Dr. Zongqi Xia from BWH’s Ann Romney Center for Neurologic Diseases.
Participants were initially asked to complete a web-based survey questioning their medical history, family history, environmental exposures and other details. All study participants were asked to submit a saliva sample 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 the study’s co-senior author, Dr. Daniel Reich, of the Division of Neuroimmunology and Neurovirology at NINDS. “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.”
First-degree relatives are 20 to 40 times more prone to developing MS compared with the general population. Consistent with the notion that much of the disease is asymptomatic, clinically silent MS-like brain lesions are seen in 4 to 10 percent of MS family members. However, screening all MS family members with serial neuroimaging is not practical because the absolute risk of the disease remains modest, with estimates indicating that of 10,000 first-degree relatives, only about 62 will be diagnosed with MS over five years.
In their initial analysis, the researchers tested a method that calculates an individual’s risk for developing MS, and also identified a subset of family members that may be at increased risk for MS compared to the average family member.
“This report is an important first step. 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,” De Jager said. “Overall, the risk of MS remains very small for most family members. 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.”