Understanding the role iron plays in MS progression
In relapsing MS, symptoms are often a result of new lesions – areas of inflammation and damage in the brain. But we know people's symptoms can gradually get worse even when they aren't having a relapse and their MRI scan doesn't show any new lesions.
You might see this referred to as 'smouldering' MS or progression independent of relapse activity (PIRA).
Paramagnetic rim lesions (PRLs) are areas of chronic inflammation in the brain. They have a dark rim of iron at their edge and are linked to a higher risk of disability. Studies also suggest that inflammation throughout the brain could lead to the buildup of iron, which could be toxic and contribute to disability progression. But typical MRI scans have limited ability to show what's happening outside of lesions.
This project will explore whether widespread inflammation and iron accumulation in the brain are linked to disability progression in MS.
About the project
In this project, Dr Marco Pisa and his team will use a variety of techniques. They'll explore how inflammation and iron buildup in the brain might be interacting to drive MS progression.
- Firstly, using brain and spinal cord tissue from the MS Society Tissue Bank, they'll look at inflammation and iron in the brain under a microscope. And identify whether they're limited to certain areas, or widespread throughout the brain.
- Secondly, using a large dataset containing MRI information from over 500 people with MS, they’ll look at the number and location of PRLs. Currently, the number of PRLs is used to predict how someone’s disability might progress. Dr Pisa and his team will test whether factoring in the location of the lesions can improve these predictions. They'll also create a map of iron distribution throughout the central nervous system. And look to see if this is linked to the prevalence of PRLs.
- Finally, they'll take MRI scans of spinal cord tissue and compare this with their microscope analysis. This could help them identify markers on MRI scans that are associated with the build-up of iron.
How will it help people with MS?
There are over 20 disease-modifying therapies for people with relapsing remitting MS. But now we have drugs that control relapses so well, it’s become clearer that anyone with MS could have disability that’s not related to relapses. It's not just people with progressive MS.
Understanding more about the processes in the brain that contribute to MS progression could help open new avenues for treatments.
