A group of international scientists studying multiple sclerosis has identified what they believe to be the first genome-wide variant capable of accelerating degeneration associated with the disease.
While this gives MS researchers a new lead to investigate treatments the scientists also identified environmental factors which can hinder the body’s fight against MS progression.
MS is a disease where the body’s central nervous system falls victim to a mistaken immune response that attacks myelin – the protective shield that insulates nerves, in turn leading to scarring that disrupts them from sending important signals.
Eventually, this can lead to changes in motor, cognitive and sensor functions.
But it’s also mysterious, often diagnosed in the absence of other clinical disorders and with no cure, a single cause remains elusive, with a range of genetic and environmental factors linked to its onset.
No two cases of MS are the same, which co-senior author of the paper published in Nature, Sergio Baranzini, says makes understanding risk factors for the disease challenging for researchers.
“[Such] risk factors don’t explain why, 10 years after diagnosis, some MS patients are in wheelchairs while others continue to run marathons,” says Professor Baranzini.
The study of 22,000 people with MS doesn’t elevate a particular genetic candidate as the disease’s cause either; it analysed more than seven million genetic mutations and pinpointed a single variant associated with a significant acceleration in MS onset.
How scientists decide which mutations in your DNA are deadly
Among the MS patients, the study found homozygous carriers of the rs10191329 variant required a walking aid faster than those without. Homozygous gene carriers possess two copies of a gene: one inherited from each parent.
Importantly, rs10191329 is located between two genes – DYSF, which is involved in cell repair and ZNF638, involved in viral infection control – which have not been linked with MS previously.
But rather than being part of the body’s immune function, these genes are, according to the study’s lead researcher Dr Adil Harroud from the University of California San Francisco, active in the central nervous system.
“Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies,” Harroud says.
This gives MS researchers a new lead to investigate treatments that might stymie disease progression. The research consortium, which was led by UCSF and Cambridge University, will now look at how rs10191329 impacts its neighbouring genes and the human nervous system.
Among other findings, the researchers determined several environmental factors that can hinder the body’s fight against MS progression.
This, they saw, emphasises the importance of resilience against neurone degeneration.
Smoking was found to have a potential causal effect on worsening disability. Education level was found to improve resilience to MS progression, specifically, four years of extra learning – described by the researchers as the equivalent of an undergraduate degree. This, the study suggests, might be due to a concept called ‘neurocognitive reserve,’ where genetic and environmental factors can impede neural decline due to aging.
“Although it seems obvious that your brain’s resilience to injury would determine the severity of a disease like MS, this new study has pointed us towards the key processes that underlie this resilience,” says the study’s other co-senior author, Professor Stephen Sawcer of Cambridge University.
The results were first presented by Baranzini in scientific sessions of last year’s European Committee for Treatment and Research in Multiple Sclerosis in Basel, Switzerland. The research has been published today in the journal Nature.