- This is the first study to suggest that certain genes may influence disease severity in those with MS.
- The researchers evaluated the health data of over 22,000 people with MS to conduct a genome-wide association study.
- The team identified one variant, that was linked to quicker disease progression.
Researchers from the University of California, San Francisco have identified a genetic variant that may cause some patients with multiple sclerosis (MS) to develop more severe symptoms compared to others with the disabling neurological disease.
The study, published in Nature on June 28, found that a specific genetic variant, located between genes responsible for cell repair and infection control, may speed up the progression of the disease, and result in a patient needing a walking aid more quickly, by as much as four years.
This is the first report to suggest that certain genes may influence disease severity in those with MS.
Past research has shown that MS is rooted in dysfunction of the immune system, but it’s been unclear why some patients are unable to walk a decade after being diagnosed with MS whereas others continue to have normal mobility for years.
“We see this clinically all the time, and it is very exciting that researchers are beginning to unravel this. These findings will open up new targets and pathways for future drug development, although this is likely some way off,” Christopher Lock, MD, a clinical associate professor of neurology and neurological sciences at Stanford Medicine, told Healthline.
Lock was not part of the study.
The researchers evaluated the health data of over 22,000 people with MS to conduct a genome-wide association study, which is a research technique that links genetic variants to specific traits.
The team investigated which genetic variants were linked to disease severity, along with the speed of disease progression, or how much time it took for a person to advance from diagnosis to various levels of disability.
Over 7 million genetic variants were analyzed and the team identified one variant, labeled rs10191329, that was linked to quicker disease progression.
“Individuals that carry two copies of this variant had increased brain damage, as seen on autopsies,” says Adil Harroud, MD, the lead author of the study and a neurologist specializing in multiple sclerosis research at McGill University.
It sits between two genes, DYSF and ZNF638, that haven’t previously been connected to MS.
DYSF helps repair damaged cells and ZNF638 helps manage viral infections.
The researchers suspect the variant’s close location to these genes — and its effect on cell repair and viral infections — contributes to the speed at which MS progresses.
“Based on these functions, it is possible that this genetic variant makes MS worse by affecting how well brain cells repair themselves after an immune attack. It might also affect how well one can control viral infections, such as EBV, that could be driving some of the pathology,” Harroud said.
MS appears and progresses differently from person to person.
“Some people have prominent motor symptoms, others have less visible symptoms such as cognitive difficulty, and some have spinal cord lesions,” says Lock.
There are risk factors that are associated with a worse prognosis in people with MS, including older age, low vitamin D levels, obesity, smoking, being male, African American, or Hispanic.
It’s difficult to predict the course of MS in a particular individual, according to Lock.
There are several theories that have been proposed to explain what drives disease progression, including inflammation and neurodegeneration.
“While all these processes likely contribute to the accumulation of damage in MS, a longstanding and unresolved question is whether differences in MS severity between individuals are driven most by the behavior of their immune system, or by how the brain and spinal cord are responding to those injuries,” says Harroud.
The new findings suggest that certain genes in the brain and spinal cord are most strongly associated to disease severity in MS patients, he added.
The researchers hope the identification of this variant can help inform future treatment methods that can slow down how quickly MS advances in certain patients.
“Currently available medications for MS prevent further inflammatory damage, but there is unmet need in the area of progressive forms of MS, as the authors note,” says Lock.
Repair and regeneration will be an important element of future treatments.
“By identifying specific genes or gene versions that are associated with MS severity, we can learn more about the underlying biological processes that contribute to accumulating disability in MS,” Harroud said.
With that information, scientists could develop a drug that targets the affected genes.
If someone carries these genetic markers, a higher efficacy medication could be considered early in their disease, says Lock.
There’s currently no genetic test MS patients could get to see if they have this genetic mutation.
According to Harroud, most people with MS, over 80%, do not have this variant.
“If someone has MS and wants to help us learn more about the genetics of MS, they can contact local MS centers who are part of these international studies,” Harroud said.
Researchers have identified a genetic variant that may cause some patients with multiple sclerosis to develop more severe symptoms compared to others with the disabling neurological disease. This is the first report to suggest that certain genes may influence disease severity in those with MS, and researchers hope the findings may help scientists develop more effective treatments for MS.