The impact of inflammation on DNA damage in brain cells in primary progressive MS

Associate Professor Justin Rubio

University of Melbourne, VIC

February 2023

specialisation: Neurobiology

focus area: Better treatments

funding type: Project

project type: Investigator Led Research

Summary

Damage to the DNA in our cells is a natural part of the ageing process. Previously, Associate Professor Justin Rubio and his team proposed that inflammation in the brains of people living with MS could potentially accelerate DNA damage in neurons and oligodendrocytes (myelin-producing cells). They proposed that this could play an important role in neurodegeneration and progressive MS.   

Their preliminary work suggests that this may indeed be the case and that people living with primary progressive MS may be more affected than others.  

This project aimed to replicate these initial findings with a view to providing a better understanding of the role of DNA damage in primary progressive MS and downstream opportunities for developing treatments. 

Outcome

Associate Professor Rubio and his team have made substantial progress on this project. 

To determine whether DNA damage to nerve cells in the brain of a person with progressive MS has the potential to contribute to nerve damage and disease progression, Associate Professor Rubio and his team analysed the genes of 106 nerve cells from post-mortem brain tissue of 10 people with MS and 16 without MS. 

The team found that nerve cells located in chronic lesions (old lesions) in the brain of a person with MS had excessive DNA damage, which shows as more gene mutations than someone who doesn’t have MS. This damage accumulates one-and-a-half times faster in nerve cells within lesions compared to nerve cells in other regions of the brain. These excessive mutations were observed in people with progressive MS, and the team believes that this is due to inflammatory processes that occur in the brain of someone MS. This could have an impact on the function and survival of nerve cells. 

Using advanced computational methods, Associate Professor Rubio and his team discovered specific patterns of mutations that tell us about the biological processes that contribute to DNA damage, which may in turn affect MS progression. 

While further work is required to follow up on these findings, these results provide evidence that DNA damage to nerve cells caused by inflammation in the brain may be an important mechanism for nerve damage and MS progression. 

Associate Professor Rubio has received an MS Australia Senior Research Fellowship to extend this work. 

Updated 31 March 2024

lead investigator

total funding

$250,000

start year

2023

duration

1 year

STATUS

Past project

Stages of the research process

Fundamental laboratory Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline

10+ years

Translational Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline

5+ years

Clinical Studies and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline

3+ years

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The impact of inflammation on DNA damage in brain cells in primary progressive MS