Moving MS Genetics Forward To a World Free of MS
Ending MS can’t come fast enough and one key to ending MS is our focus on genes that help make people susceptible to developing MS. Research suggests that MS occurs in individuals and in families whose genes make them susceptible, and that many genes contribute to MS susceptibility. In addition, individuals who are genetically at risk must encounter some other triggering factor or factors in their environment to actually develop MS.
Pinpointing and understanding “MS genes” is important because
• it will provide key information regarding the cause of the disease and therefore how to prevent it
• genes that are associated with MS may be targets for the development of new therapies
• if we could identify those people who have a strong genetic predisposition to the disease, we might be able to intervene at its earliest stages or prevent MS.
Ending MS: Making it happen
The MS DNA Bank
With funding from the National MS Society, the University of California at San Francisco established a DNA bank in 1997 that spearheaded multiple successful collaborations to identify variants in the genome that influence the individual’s risk to develop multiple MS. With further Society funding, the DNA Bank is now maintaining and expanding its core DNA repository of MS patients, family members and unrelated controls, linking it to a sophisticated database for the storage of detailed clinical, demographic, and laboratory data. This Bank provides an outstanding opportunity to identify and characterize MS-related genes, which may translate into clinically useful genetic biomarkers and reveal novel targets for new therapies. You can participate in these genetic studies.
The International MS Genetics Consortium
The next generation of MS genetics began when the International MS Genetics Consortium (IMSGC) was launched with early seed funding from a National MS Society Collaborative MS Research Center Award. The IMSGC brings together MS genetics researchers from 15 countries who collaborate and share results openly to spur progress. In 2007, the IMSGC published a groundbreaking initial genome-wide study that clearly identified two new genes that predispose people to developing MS. Just seven years later, after studies involving over 100,000 people, the IMSGC has identified 200 genetic variations related to MS, and has begun to identify the specific immune cells and proteins involved. These teams could not have accomplished this massive task if not for this international collaboration.
• Interpreting the genetic variations identified by the IMSGC and other large-scale studies remains a challenge. One team developed a sophisticated mathematical model to tackle this problem, mapping identified gene variations to the activity of 56 different cell types. Duke University researchers funded by the Society are using new technologies to identify MS risk genes that are important in particular types of immune cells. The strategies used by these investigators offer a roadmap for tracing the influence of genes on cell activity and new insights for preventing MS. Yale researchers newly funded with a Collaborative MS Research Center Award from the Society are assembling a talented team that will use highly advanced technology to manipulate genetic information in cells that are active in the immune attack in MS; these experiments will help tease out the exact pathways by which MS develops.
• Predicting MS risk: Harvard researchers funded by the Society are developing an individualized risk prediction tool that incorporates the latest knowledge in MS genetics and may be able to predict a person’s risk for developing MS. Team leader Philip L. De Jager, MD, PhD, received the 2014 Barancik Prize for Innovation in MS Research, for his work in applying powerful analytic approaches to better understand how genes and the environment interact. A second team from Harvard is analyzing the large number of gene variations that contribute to the risk of getting MS, but not other autoimmune diseases, to find important ones to target for new therapies and clues for prevention.
• The interaction of genes and environmental factors is being investigated: The Network of Pediatric MS Centers is studying children with early relapsing-remitting MS to determine environmental and genetic risk factors that make children susceptible to developing MS. In early findings, low vitamin D status, which has been linked to MS risk, was associated with MS relapses only if kids had a specific immune gene. A University of Vermont team funded by the Society is looking at genes that may interact with Vitamin D to influence susceptibility to MS-like disease in mice. Researchers from the Harvard Medical School are studying 5,000 subjects who have at least one first-degree relative with a diagnosis of MS to identify the genetic, environmental and immune profiles that may increase a person’s risk of developing MS.
• Focusing on ethnic groups with varying levels of susceptibility to MS may help to understand the clinical differences between ethnic groups, and help pinpoint regions that contain MS genes. A nationwide team of researchers funded by the Society conducted the largest genetic study of people with MS of non-European ancestry, screening for known gene variants in more than 1,000 African Americans with MS, and showing significant differences that may help sort out why MS is often more severe for African Americans. Join this effort. University of Miami researchers funded by the Society are establishing a unique dataset containing demographic, neurologic, and genetic material from a large cohort of Hispanic Latinos with MS. They are examining known genes that influence MS and looking for new genes that may be involved in MS specifically in the Hispanic population.
• The Society is driving commercial progress toward development of a simple blood test that would use genetic information to diagnose MS. This includes a partnership with Lineagen to establish and validate a broad array of biomarkers for MS; and a partnership with Diogenix to develop a DNA “signature” for MS that might be used to identify MS early in the disease course.
• Following gene clues to find new therapies: Taking a first step toward translating this gene data, a team from Harvard and MIT has begun examining how MS genes identified to date interact with the “druggable genome” – a data set of existing therapeutics. So far they have identified more than 2,000 possible therapeutic interactions. Such studies are key to mining genetic information for therapeutic strategies.