Using human genomics to identify drug targets for progressive MS

Over the past year, Associate Professor Rubio and his team have furthered their understanding of how microglia—the brain’s resident immune cells—may drive MS progression. Recent studies of Alzheimer’s disease show that somatic mutations (genetic changes that occur after birth) in microglia can promote harmful inflammation. There are also current trials in progressive MS that target microglia, including trials of Bruton’s tyrosine kinase (BTK) inhibitors.

The team has refined their methods for isolating microglia nuclei (that contain the genetic material) and applying highly sensitive DNA sequencing techniques. They have analysed brain tissue from three MS Australia Brain Bank tissue donors with MS and compared areas of damage (lesions) with healthy tissue. The researchers found unique somatic mutation patterns in microglia from lesions compared to non-lesion brain tissue. Using the methods developed in the first year of this project, Associate Professor Rubio was also awarded an MS Australia Incubator Grant.

This year, Associate Professor Rubio and his team will focus on isolating microglia nuclei and sequencing and analysing data from lesions and non-lesion tissue from a further 10 MS Australia Brain Bank tissue donors. This research could open new avenues of investigation for treating progressive MS. Progressive MS is a very important treatment challenge facing the MS community. Access to effective treatments to slow down or prevent MS progression will improve the quality of life for people living with MS.