Close relatives of MS patients face 100 times higher risk of developing disorder
Study findings support feasibility of trials aimed at preventing disease
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- Close relatives of multiple sclerosis patients have a 100 times higher risk of developing the disorder.
- Genetic and environmental factors contribute to multiple sclerosis risk.
- Many at-risk individuals are willing to participate in prevention trials.
Close relatives of people with multiple sclerosis (MS) are 100 times more likely to develop the neurological disorder than the general population, according to a new analysis of GEMS data.
Among participants in GEMS, a large-scale observational study assessing MS risk among family members, about half said they would participate in a clinical trial aimed at preventing MS. That number rose to three-quarters if genetic testing indicated they had a higher risk of MS.
“Our findings support the feasibility of primary prevention trials in individuals at risk for MS and pave the way for the first generation of such studies to be designed,” the scientists wrote.
The study, “A Prospective Study of Individuals at Risk of Multiple Sclerosis Informs the Design of Primary Prevention Studies,” was published in the Annals of Clinical and Translational Neurology. It was funded by the National MS Society.
Early data showed relatives’ risk of developing MS was 30 times higher
MS is a chronic disease that affects the brain and spinal cord, causing inflammation and nerve damage. It’s thought to arise from a combination of genetic and environmental risk factors, including smoking, obesity, low vitamin D levels, and past infection with the Epstein-Barr virus.
Launched in 2011, the GEMS study (NCT01353547) is following first-degree relatives (parents, siblings, or children) of people with MS to determine their risk of developing the disease. Participants provided saliva samples for DNA testing and completed questionnaires on medical history, family history, and environmental exposures.
The study also developed a Genetic and Environmental Risk score (GERS) for each person by combining known genetic and environmental risk factors to identify those at highest risk of developing MS.
Early data showed that these relatives’ risk of developing MS was 30 times that of the general population, but scientists have now updated the GEMS findings for 1,903 participants who were followed for up to 11 years.
Half of participants willing to join future clinical trials
Participants completed seven questionnaires since enrollment in 2011. Among them, 8% already had an MS diagnosis at enrollment, and about 0.9% developed MS between the first and last questionnaires.
Based on the total follow-up time for each patient, the data suggested that 211 new cases of MS occur each year for every 100,000 symptom-free relatives. In other words, roughly 1 in 500 participants per year developed MS, with the average age at diagnosis of 33.
Researchers noted that the incidence of MS among family members of MS patients was 100 times greater than the reported incidence of MS in the general population.
When the team examined GERS scores, they found that people who already had MS at enrollment had significantly higher risk scores than family members who did not have the disease. However, no clear differences in risk scores were seen between people who later developed MS during the study and those who did not.
Scientists also tested an updated genetic-only risk score that included 224 genetic markers linked to MS, up from 64 in the earlier version. The updated score closely matched the earlier one, suggesting both methods measure MS risk similarly. The predictive accuracy was moderate and similar for both the genetic-only score and the combined GERS score.
Primary prevention trials in MS are urgently needed. Our findings support the feasibility for such studies and inform the design of future primary prevention trials in individuals at risk for MS.
When participants were asked whether they would be willing to join a future clinical trial aimed at preventing MS, nearly half (48%) said yes. Almost all (90%) said they would be willing to provide a blood sample for a genetic test to determine their personal risk of developing MS. If the test showed an increased risk of MS, the number willing to join a trial rose to 75%.
Among those interested in joining a study, most (89%) were willing to try existing, approved vaccines, followed by approved daily oral medications (67%). Willingness was even higher if participants believed they had a higher risk of developing MS.
Although interest was somewhat lower for new or experimental treatments, most participants still said they would consider joining studies testing new vaccines (64%) or oral medications (58%).
“Primary prevention trials in MS are urgently needed,” the scientists wrote. “Our findings support the feasibility for such studies and inform the design of future primary prevention trials in individuals at risk for MS.”
