A study of more than 22,000 people with multiple sclerosis (MS) has, for the first time, identified a genetic variant associated with faster progression of the disease.
The findings could lead to new drugs that may help preserve the health of people who live with MS, according to researchers.
MS begins as an autoimmune disease where the immune system attacks the brain and the spinal cord. This results in symptom flares, called relapses, as well as longer-term degeneration known as progression.
Unfortunately, although there are effective treatments, none can prevent increased disability during the neurodegenerative phase.
The new study, which includes researchers from Yale and was published in the journal Nature, is the first to identify a genetic variant that increases disease severity. The study authors say this advance is a key step toward understanding and eventually fighting the progressive form of MS.
“While we have identified genetic variants that are predominantly immune related [and] associated with risk of developing MS, this is the first study to identify neuronal genetic variants associated with the neurodegenerative aspects of the disease,” says Dr. David Hafler, chair of Yale’s Department of Neurology and an author of the study.
The work was the result of the International MS Genetics Consortium (IMSGC), which consists of more than 70 institutions from around the world. Hafler is a co-founder of the IMSGC.
Previous studies have shown that the risk of developing MS stems in large part from dysfunction in the immune system. Some of this dysfunction can be treated, slowing progression of the disease.
But “These risk factors don’t explain why, 10 years after diagnosis, some MS patients are in wheelchairs while others continue to run marathons,” said Sergio Baranzini, a professor of neurology at University of California, San Francisco, and co-senior author of the study.
For the first part of the new study, researchers combined data from more than 12,000 people with MS to complete a genome-wide association study.
This approach that uses statistics to carefully link genetic variants to particular traits. In this case, the traits of interest were related to MS severity, including the years it took for each individual to advance from diagnosis to a certain level of disability.
After sifting through more than 7 million genetic variants, the scientists found one that was associated with faster disease progression.
They found that the disease progressed faster in MS patients with two copies of the gene variant, located near the two genes that help repair damaged cells and one that helps control viral infection.
“Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years,” Baranzini said.
These genes are normally active within the brain and spinal cord, rather than the immune system.
Leads for Additional Research
The findings give the field its first significant leads to address the nervous system component of MS.
“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,” says Adil Harroud, assistant professor of neurology at the Montreal Neurological Institute and lead author of the study. “This gives us a new opportunity to develop new drugs that may help preserve the health of all who suffer from MS.”
This work was supported in part by funding from the U.S. National Institute of Neurological Disorders and Stroke (which is part of the U.S. National Institutes of Health), the European Union’s Horizon 2020 Research, and Innovation Funding Programme, and the Multiple Sclerosis Society of Canada. TwP