Does inflammation cause faster mutation of cells located in MS lesions?

Associate Professor Justin Rubio and his team recently published research showing that DNA from nerve cells located in multiple sclerosis (MS) brain lesions mutates at an accelerated rate compared to other nerve cells. As strong inflammation occurs in MS brain lesions, it is thought that this inflammation is somehow involved in causing mutations to nerve cell DNA, which is likely to affect the function of nerve cells and their viability.

An important unanswered question is whether inflammation is the cause of the increased mutation rate in nerve cells, or whether the nerve cells have a higher mutation rate that then triggers inflammation and the damage associated with it.

To determine whether inflammation is the cause or an effect of the accelerated mutation rate in nerve cells, this project will investigate mutation rates in DNA from cells in lesion biopsy samples from people at an early stage of their MS course. The team will then compare the mutation rate of cells from these early-stage MS lesion biopsy samples with those from post-mortem MS lesions from people who had late-stage (progressive) MS. This comparison will reveal differences in mutation patterns between early- and late-stage MS lesions, including any genes impacted more than others, and will help determine if the accelerated mutation rate is already present in cells from early-MS lesions.

Outcomes from this project will transform our understanding of the relationship between inflammation in the brain, changes in DNA that builds up in individual brain cells, and MS progression.