Researchers Discover Genetic Marker of Severity and Progression in Multiple Sclerosis

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For the first time, researchers have identified genetic determinants of disease severity and progression in multiple sclerosis (MS). The findings were recently published in Nature.

Despite an emphasis on MS research, scientists understand little about the processes leading to disease progression or relapse. Previous genetic research in MS has focused primarily on determining the role of genetics in disease predisposition and onset. To date, more than 200 loci, or specific locations within DNA, are considered to potentially increase the risk of MS. However, previous literature lacked an assessment of genetics and managing patient variability. With this in mind, researchers from the International Multiple Sclerosis Genetics Consortium and the MultipleMS Consortium conducted research focused on genetic determinants of disease severity and progression.

Investigators collected DNA from an initial 12,584 MS patients with varying degrees of disease progression. They also gathered disease severity scores while adjusting for patient-specific variables such as age. Once collected, researchers analyzed the DNA in attempt to identify specific loci within the DNA closely that were associated with more severe or more progressive disease.

Importantly, the team collected information on an additional 9,805 patients to ensure their results could be replicated in a different population. After analyzing data from the second set of patients, two loci of interest were identified.

The first locus was attributed to MS progression. In those with typical genetic code in this location, MS progression occurred as expected. However, in those with a mutation in this specific location, disease progression occurred more rapidly. While this locus presents opportunities for further research, no specific information regarding a mutation’s role in progression could be determined.

The second locus, however, provided more insight. In those with mutations in the second locus, the median time until needing a walking aid decreased by 3.3 to 3.7 years, depending on the genetic variant present.

The authors described the magnitude of this genetic influence as similar to that of disease-modifying treatment (DMT) for MS. While DMT drugs such as beta-interferon have been shown to delay disability and the need for a walking aid by about four years, this new research suggests that possessing these mutations may accelerate the time to requiring a walking aid by a similar timeframe—essentially negating the benefit of existing DMTs for certain individuals with MS.

While this discovery provides groundbreaking evidence of genetic influence on MS, many questions remain. However, the findings provide a roadmap for future studies and potential targets for drug development.