Scientists have identified the first genetic variant associated with faster multiple sclerosis progression, potentially paving the way for new treatments.
The autoimmune disease results from the immune system attacking the brain and spinal cord, leading to damage to the insulating myelin layer that forms around nerves, and disrupting signals to and from the brain.
For many people with MS, relapses can cause symptoms to flare and result in longer-term degeneration.
The risk of a person developing the disease stems in large part from dysfunction in the immune system, which can in part be treated to slow the disease.
But until now, scientists have not understood why it progresses faster in some people.
Symptoms include numbness, tingling, mood changes, memory problems, pain, fatigue, blindness and paralysis, according to the National MS Society.
“These risk factors don’t explain why, 10 years after diagnosis, some MS patients are in wheelchairs while others continue to run marathons," said Professor Sergio Baranzini at the University of California, San Francisco, co-senior author of the study published in Nature.
But now an international team of researchers, led by UCSF and the University of Cambridge, has discovered a genetic variant associated with increased disease severity.
The results, they say, suggest resilience and repair in the nervous system determine the course of MS progression.
Cambridge University Professor Stephen Sawcer, a member of the Cambridge University Hospitals NHS Foundation Trust, said the discovery would be “transformative” in terms of a search for new treatments.
He told The National: “It accounts for less than 1 per cent of the variants. It’s a tiny proportion of the variants in this highly variable outcome.
“To give you an idea of the scale, if you inherit both alleles, if you inherit the allele from your mother and from your father… then you will need a walking stick, on average, 3.7 years, nearly four years, earlier than someone who doesn’t.
“So that’s about the same scale of effect as treatment with beta interferon, which was the first treatment introduced for MS that controls the relapsing aspects of the disease, to a degree.”
He said the discovery was important because it may vastly improve the chances of pharmaceutical companies researching a drug that aims to slow progression.
He said: “It costs billions and billions to make a drug.
"Drug companies have learned, over the last few years, and this is not just for MS, this is across the board, the target, if it’s got genetic support, is much more likely to transform into a successful treatment.
“Until today, there is no pharmaceutical company working on a drug for progression in MS in any concerted way, because it has no genetic support.
“Now we have a target, so this transforms the landscape. So now there is a serious prospect a pharmaceutical company will take this on. I think the prospects for pharma involvement and the development of a drug have transformed today.”
Looking at statistics from The International Multiple Sclerosis Genetics Consortium (IMSGC) and The MultipleMS Consortium, researchers assessed genetic factors influencing MS severity.
They combined data from 12,584 people with MS, linking genetic variants to particular traits, such as the time it took for each individual to advance from diagnosis to a certain level of disability.
After sifting through 7.8 million genetic variants, one was found to be associated with faster disease progression.
Dr Adil Harroud, lead author of the study and former postdoctoral researcher in the Baranzini Lab at UCSF, added: "These genes are normally active within the brain and spinal cord, rather than the immune 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."
