Primary progressive MS risk may be linked to genes that cause other brain diseases 

• Genetic screening of people with primary progressive MS has shown that four rare genetic changes, which are known to cause other neurological diseases, may play a role in primary progressive MS
• Primary progressive MS is a less common form of MS, in which disability accumulates from the outset of the disease rather than the intermittent ‘attacks’ seen in relapsing-remitting MS
• Until now, genetic research has not identified any genetic changes specific to this type of MS
  Genetic screening of people with primary progressive MS has now identified that four rare genetic changes, known to cause other neurological diseases, may be playing a role in primary progressive MS
• Genetic changes related to a neurological disease called spastic paraplegia were also found to be more common in people with progressive MS
• These new genetic discoveries may help provide clues as to why some people develop the primary progressive form of MS and possible treatment approaches to slow or stop disability accumulation

Although many genes that contribute to the risk of developing MS have been discovered, research has not yet identified genes that are specifically linked to the risk of developing the primary progressive form of MS. Now, a new international study has shown that rare changes to genes that cause other brain diseases may also play a role in primary progressive MS.

Primary progressive MS is a less common form of MS, in which disability accumulates from the outset of symptoms. This type of MS tends to be diagnosed later in life than the more common relapsing-remitting form of MS. It also affects both men and women equally, whereas relapsing MS affects two – three times more women than men. To date, there have been no clues as to why some people develop the progressive forms of MS.

Many large international studies have asked the question of whether a person’s genes may affect their risk of developing MS and it is now known that over 200 genes are involved in the risk of developing any kind of MS. However, genes specifically linked to the risk of developing primary progressive MS have not yet been identified.

Rare changes

A new international study sought to identify whether rare changes to genes might be linked to primary progressive MS. The researchers focused specifically on those genes known to cause other neurological disorders that have symptoms similar to progressive MS.

The first stage of the study involved screening all of the genes from 38 people with primary progressive MS and 81 people without MS. This screen identified 15 genetic changes that were likely to be meaningful for progressive MS.

Whilst small differences do exist between different people’s DNA codes, in this study, the researchers identified that the changes were rare DNA changes not found in the majority of people and were likely to cause damage to the functioning of certain types of cells. These genetic changes were also known to be linked to other neurological disorders. Importantly, the changes were not present in the people who did not have MS.

Further study

To confirm whether or not these genetic changes were genuinely linked to primary progressive MS, the researchers investigated how commonly these changes were found in a larger group of people with primary progressive MS and people without MS. They also looked for the changes in a group of people with relapsing forms of MS, in order to identify whether the genetic changes were specifically linked to progressive MS or simply part of the genetic ‘story’ for all people with MS.

In the results, four of the 15 gene changes were identified as specifically important for primary progressive MS. These changes were linked to a number of disorders with gradually worsening neurological symptoms, including spastic paraplegia, megalencephalic leukodystrophy with subcortical cysts and tuberous sclerosis.

Since two of the changes were related to spastic paraplegia, the researchers proceeded to analyse whether other genetic changes linked to that disease are more common in people with primary progressive MS. They looked at 169 genetic changes related to spastic paraplegia and found that they were more common, not only in people with primary progressive MS, but also people with secondary progressive MS. The gene changes were far less likely to be found in people with relapsing-remitting MS, suggesting that these genetic changes are contributing specifically to the risk of a person developing a progressive MS disease course.

Determining the role of genes in influencing whether an individual’s MS will take a progressive course is hugely important in understanding the biology of progressive MS and will help researchers to identify new treatment options that could slow or stop the accumulation of disability for people with progressive MS. The next step will be to look more closely at the biological functions of these genes and identify exactly how they make people more vulnerable to developing progressive MS.

With thanks to MS Research Australia – the lead provider of research summaries on our website.