Investigating cell and blood vessel damage in MS

Ms Lillian Toomey

Curtin University, WA

January 2019

specialisation: Neurobiology

focus area: Better treatments

funding type: Scholarship

project type: Investigator Led Research

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.

Outcome

Dr Lillian Toomey’s research has made significant progress in the understanding of the mechanisms of myelin damage in both brain trauma (neurotrauma) and MS. In a neurotrauma cohort, the data analysis revealed that early damage to vulnerable oligodendrocyte precursor cells, which play a crucial role in myelin production, was associated with blood vessel dysfunction. This finding suggests that early damage to these cells may lead to myelination problems following injury. Ongoing research is now investigating whether a similar vulnerability of these cells occurs in an MS model. 

In an established laboratory model of MS, Dr Toomey conducted a trial using a scientific compound to induce the disease. However, she found that the compound’s effectiveness was not as expected. As a result, Ms Toomey explored alternative options and identified important differences between different formulations of the compound. This discovery has led to a significant publication in the field, which has been widely referenced, highlighting its importance in optimising the MS model. 

Another crucial aspect of the project involves understanding the mechanisms of myelin damage in MS compared to other types of nerve injuries. The research team is currently analysing brain tissue from a trauma model of nerve damage to examine how cellular damage affects blood vessel function in both MS and traumatic injuries. They have developed a method to prepare and image the brain tissue for analysis of specific tissue features. This analysis is ongoing, and the findings will be reported once completed. 

This research sheds light on additional mechanisms that contribute to brain and spinal cord damage in MS. These findings could pave the way for the development of innovative therapies targeting myelin damage in MS. The progress made by Dr Toomey so far holds promise for uncovering new avenues for the treatment of this debilitating condition. 

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
  • Toomey, L.M., Papini, M.G., Clarke, T.O., Wright, A.J., Denham, E., Warnock, A., McGonigle, T., Bartlett, C.A., Fitzgerald, M. and Anyaegbu, C.C., 2023. Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats. International Journal of Molecular Sciences, 24(4), 3463. doi.org/10.3390/ijms24043463
  • Gopalasingam, G., Bartlett, C.A., McGonigle, T., Majimbi, M., Warnock, A., Ford, A., Gough, A., Toomey, L.M. and Fitzgerald, M., 2019. The effects of a combination of ion channel inhibitors on pathology in a model of demyelinating disease. Multiple Sclerosis and Related Disorders, 34, 1-8. doi.org/10.1016/j.msard.2019.06.005

Updated: 31 March 2023

lead investigator

Ms Lillian Toomey

total funding

$90,000

start year

2019

duration

3 years

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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Ms Alice Saul

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Investigating cell and blood vessel damage in MS