First genetic marker linked to multiple sclerosis severity identified

An international team of scientists has identified the first genetic variant associated with the severity of multiple sclerosis (MS), which could lead to new treatments to prevent the disabilities caused by the progression of the disease.

The paper was published in the prestigious science journal Nature on Wednesday.

The study's lead author, Dr. Adil Harroud, assistant professor at the Montreal Neurological Institute of McGill University, calls it an exciting discovery.

"We just did not know before this study whether genetics had any role to play and why some people fare worse with MS," the neurologist said.

"There are certainly a lot of implications. Canada, as a country, has the highest rate of MS in the world," he added.

TALKING ABOUT MOBILITY

The lifelong condition is understood to be a result of the immune system mistakenly attacking the brain and spinal cord.

MS causes a slew of symptoms that can come and go, including fatigue, and problems with vision balance, movement and others.

"Here, we're talking about mobility," said Harroud.

"We're still a long way from understanding why some people have worse MS compared to others, and why 10 years into their disease, some people may be in a wheelchair, whereas others are still able to run marathons," he said.

Now they have some new genetic evidence to help them start to answer the question.

More than 70 institutions collaborated on the study which involved 22,000 people with MS.

Scientists sifted through their genetic code to find the first genetic variant associated with faster disease progression, which amounts to the accumulation of disability that robs patients of their mobility and independence.

If a patient with MS has inherited two of the variants they become disabled at an accelerated pace the study also found, requiring a walking aid four years earlier than a patient with only one variant, for example.

"This gene variant does not increase your risk of MS, it just increases your risk of doing poorly if you happen to also have MS," said Harroud.

Identifying the variants associated with MS severity will help scientists learn more about the underlying mechanisms that contribute to progressive disability.

"And then our hope is to develop a drug that targets those same gene mechanisms and then results in slowing or stopping MS progression. That's something that our current therapies are not capable of doing," said Harroud.

The location of the newly discovered genetic variant is also intriguing -- it resides between two genes called DYSF and ZNF638, which had no prior connection to MS.

The first one is involved with repairing damaged cells and the second helps to control viral infections, said a press release issued by the University of California San Francisco (UCSF), one of the lead institutions on the study, along with the University of Cambridge.

"What this tells us is that we need to now direct our efforts in understanding brain resilience and repair so that we can develop therapies that are focused on these mechanisms," Harroud said.

GENETIC DIVERSITY

Harroud also said that it's important to be mindful of genetic ancestry, during the study of genetics.

"The highest number of people that contributed to the study were people of European genetic ancestries. And we were able to include African American individuals and Latin and Hispanic individuals and East Asian individuals," he said.

"But we didn't have enough numbers to confirm our findings in these diverse ancestries. And it is very important for us to be able to generalize these findings to non-Europeans as well. So this is something that we're working towards --increasing the representation of people with MS in our studies," said Harroud.