Investigating cell and blood vessel damage in MS

Ms Lillian Toomey

Curtin University, WA

| Better treatments | Neurobiology | Scholarship | 2019 | Investigator Led Research |
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Summary

MS has traditionally been considered to be caused by immune cells from the body entering the brain and attacking myelin, a fatty layer that protects our nerve cells in the brain and spinal cord. It is also thought that these immune attacks can damage cells called oligodendrocytes that produce myelin. However, treatments targeting the immune attack are not always effective, which may suggest that there are other mechanisms contributing to MS disease progression.

One possibility is that in MS, there is an increase in chemicals known as reactive oxygen species, which are naturally occurring chemicals that are by-products of normal cellular processes. However, if these processes are not fully controlled, they can cause damage to human cells. This is referred to as oxidative stress or damage, and can lead to damage to oligodendrocytes. Oxidative stress has been studied in other neurological conditions such as Alzheimer’s disease and brain trauma, however this has not yet been deeply studied in MS.

Progress to Date

This project is investigating the role of oxidative damage in disrupting the “blood brain barrier”, which normally prevents immune cells from entering the brain; as well as the role of reactive oxygen species in damaging the myelin coating around nerve cells.

Ms Toomey completed a trial in an established laboratory model of MS. However, she found that the effectiveness of a scientific compound used in the model to induce disease was not as expected. This has led to Ms Toomey exploring other options and she has discovered important differences between different formulations of this specific scientific compound. This has led to an important publication in the field, which has been highly referenced, indicating it is an important development in optimising this model of MS.

Another component of this project is understanding the mechanism of myelin damage in MS compared to other types of nerve injury. This work will help determine how cellular damage disrupts the function of blood vessels in both MS and in traumatic injury to the nerves. The team is currently analysing the brain tissue from a trauma model of nerve damage to tease out these processes and compare them to those at work in MS. Significant technical work has been completed to develop a method for successfully preparing and imaging the brain tissue for analysis of specific tissue features. This analysis is now underway, and we look forward to report on the findings of this section of work once it is completed.

It is hoped this work will shed light on whether there are additional mechanisms damaging the brain and spinal cord in MS. If confirmed, this could reveal exciting new avenues for development of new therapies to combat myelin damage in MS.

Publications

  • Warnock A.*, Toomey L.M.*, Wright A.J., Fisher K., Won Y., Anyaegbu C., Fitzgerald M. 2020. Damage mechanisms to oligodendrocytes and white matter in central nervous system injury: The Australian context. Journal of Neurotrauma 37(5): 739-769. doi.org/10.1089/neu.2019.6890 (*equal contribution)
  • Toomey L.M., Papini, M., Lins, B., Wright, A.J., Warnock, A., McGonigle, T., Bartlett, C.A., Hellewell, S.C., Anyaegbu, C., and Fitzgerald, M. 2021. Cuprizone feed formulation influences the extent of demyelinating disease pathology. Scientific Reports, 11(1), 1-16. doi.org/10.1038/s41598-021-01963-3

Last updated: 31 March 2022

Updated: 03 January, 2019

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: 1-5 years

Investigator

  • Ms Lillian Toomey

Grant Awarded

  • Postgraduate Scholarship

Total Funding

  • $90,000

Duration

  • 3 years

Funding Partner

  • MSWA
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Investigating cell and blood vessel damage in MS