Using a new statistical tool to identify markers and mechanisms of progression
We still don’t have a full understanding of what drives progressive worsening of disability in MS. This makes it difficult to predict how someone’s disability will progress.
Researchers think that how quickly disability worsens in MS is affected by our genes. But so far, only one gene has been identified that drives it. And that gene is found in only 2.5% of people with MS. So we need tools that are better able to detect genes relevant to MS disability.
One challenge is that current statistical tools analyse data by taking an average across large groups of people with MS. This can hide important differences between individuals with MS. For example, if you have two groups of 100 people with MS, using averages gives you a single disability score for each group. So all the unique details about each person are lost.
Researchers have developed a new statistical method, called GIFT, that uses all the individual disability scores instead of reducing everyone’s information to an average single score. ‘GIFT’ stands for Genomic Field Informational Theory.
This makes the results more precise and able to detect small but meaningful differences that traditional methods miss. But this tool has never been use to understand MS progression.
About the project
In this study, the team will apply GIFT to three different types of MS data, each capturing a different aspect of disability in MS:
- Clinical data from around 1900 people with MS from Wales, including EDSS scores over time.
- Using a type of imaging from 171 people with MS, which scans important cells in the back of your eye. These cells are closely linked to brain functioning such as nerve cell loss and myelin changes.
- Brain tissue data from laboratory studies measuring gene activity in 1.6 million brain cells from 104 people with MS and 73 people without MS.
Using their GIFT tool with these three types of data, the team believe they’ll be able to identify genes and pathways that drive worsening of MS disability. They’ll also assess whether these genes can be targeted using drugs currently in development.
How will it help people with MS?
The study aims to identify more sensitive markers of MS progression. This could make it easier to identify people who are at higher risk of faster progression and improve the detection of subtle changes in clinical trials for progressive MS.
The researchers believe their results will guide the selection of drugs already used in other conditions to be repurposed in clinical trials like Octopus. If they identify genes involved in MS progression, they can then look for drugs that act on those pathways.
In the longer-term, the results could identify new mechanisms involved in nerve damage, which could then influence the development of new MS-specific drugs that target those mechanisms.
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