Researchers have discovered a genetic variant that appears to influence the speed at which multiple sclerosis (MS) progresses, potentially paving the way for new treatments.
According to the MS International Federation, about 2.9 million people worldwide have MS, a condition in which the insulating coating of the nerves in the brain and spinal cord is damaged by the immune system. The nerve fibres themselves can also become damaged.
While some people have a relapsing remitting form of the disease, others experience gradual progression that in some can cause severe disability.
Researchers say they have identified a genetic variant that appears to increase the severity of the disease. They found that people who inherit the variant from both parents need a walking aid almost four years sooner than those without.
“This is a very substantial effect for a single genetic variant,” said Sergio Baranzini, a professor of neurology at the University of California, San Francisco and co-senior author of the study. “Furthermore, this variant affects genes that are active in the central nervous system, a clear contrast to variants that confer risk [of MS], which overwhelmingly affect the immune system.”
The study, published in the journal Nature, was an international endeavour, involving 70 institutions around the world. To make their discovery, the team analysed genetic data from more than 12,000 people with MS, screening more than 7m genetic variants for associations with the speed of disease progression.
The team found that one variant, nestled between two genes called DYSF and ZNF638, was associated with a more rapid increase in disability.
The findings were backed up by further work in which the team looked at genetic data from another 10,000 MS patients, revealing those with two copies of the variant were more likely to have faster disease progression.
The team did not find an intermediate effect for people with only one copy of the variant, “suggesting that the biological effect is only conferred when both copies of the variant are present,” Baranzini said.
The team note that one of the genes adjacent to the newly identified variant is involved in the repair of damaged cells while the other is involved in the control of viral infections. Both could be affected by the variant, Baranzini said.
“The genes likely affected by this variant are highly expressed in the [central nervous system] and involved in cellular membrane repair mechanisms,” he said.
While the team note progress has been made in recent years around immune therapies that can prevent relapses, Baranzini said the new work could aid the development of therapeutics to tackle disease severity. “We think a therapy to address MS progression will be developed within 10 years,” he said.
David Lyons, a professor of neurobiology at the University of Edinburgh, who was not involved in the work, said it has been known for some time that one’s genetic makeup – particularly when it comes to genes related to the immune system – can influence the likelihood of developing MS.
“What has not yet been clear whether genetic differences between people might influence how disease progresses over time, which is largely driven by degeneration of cells of the brain,” he said.
As a result, Lyons said, the new study was hugely important. “Once we learn more about how this genetic signature affects the cells of the brain, we may identify new strategies to protect those cells from degeneration, which is the basis of the goals to slow and stop disability accumulating in MS.”
