An international team of researchers has identified the first genetic variant associated with disease severity in multiple sclerosis (MS).
In MS, the immune system mistakenly attacks the brain and spinal cord, resulting in symptom flares known as relapses as well as longer-term degeneration, known as progression. Previous studies have identified genetic factors that increase the risk of developing MS and lead to immune system dysfunction that can be treated to some extent, slowing down the disease, but these risk factors don’t explain the large variance in disease severity.
A breakthrough finding
The new genome-wide association study, led by researchers from UCSF (USA), the University of Cambridge (UK), and Karolinska Institutet (Sweden), points to a genetic variant that increases disease severity. Inheriting this genetic variant from both parents accelerated the time to needing a walking aid by almost four years.
“This is a breakthrough finding because it provides the first real progress in understanding long-term disability in MS, where patients gradually lose their mobility and independence,” says Ingrid Kockum, professor at the Department of Clinical Neuroscience, Karolinska Institutet, and principal investigator for the European part of the study. “This gives us an opportunity to develop new treatments to control progression, which is urgently needed by so many people suffering from MS.”
The variant sits between two genes called DYSF and ZNF638 with no prior connection to MS. These are normally active in the central nervous system and involved in repairing damaged cells and controlling viral infections, respectively.
“The gene variant that causes more severe MS thus appears to influence mechanisms in the brain and spinal cord, unlike genes that increase the risk of developing MS, where the immune system is central,” says Pernilla Stridh, researcher in the Kockum Lab at Karolinska Institutet and coauthor of the paper. “This implies that controlling progression might require neuroprotective agents in addition to the current anti-inflammatory standard treatments.”
The researchers also found that high education was related to slower disease progression, supporting the idea that neurocognitive reserve and brain resilience play a key role in MS severity.
The work was the result of a large international collaboration of more than 70 institutions from around the world, where two large MS research consortia joined forces: The International Multiple Sclerosis Genetics Consortium (IMSGC) and The MultipleMS Consortium.
The study included more than 22,000 people with MS, many of which were recruited in Sweden through the National MS studies GEMS, EIMS, IMSE, and COMBAT-MS that are coordinated at Karolinska Institutet.
“One of the strengths of these studies is that they can be combined with the Swedish MS registry which contains unique data gathered by neurologists throughout Sweden,” explains Dr Stridh. “This has been crucial to being able to track disease severity over time.”
Source: Karolinska Institutet
Photo of Ingrid Kockum (left): Creo Media Group. Photo of Pernilla Stridh: Magdalena Lindén