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Multiple sclerosis (MS) affects more than 33,000 Australians. While current treatments can reduce symptoms in some types of MS, they do not prevent long term damage and they do not work in all people with MS.
Nerve cells extend long conduits called axons which they use to transmit electrical signals. In healthy brains, these axons are wrapped in a substance called myelin which insulates and protects them. In MS, uncontrolled inflammation in the brain causes damage to the myelin (demyelination) leaving the axons exposed to damage, and if they are not efficiently re-wrapped with myelin (remyelination) they can be destroyed. Over many years axons and nerve cells are destroyed in people with MS, leading to permanent damage and subsequent disability. New treatments that protect and repair the brain are desperately needed to prevent this disease progression.
Microglia are caretaker brain cells responsible for regulating damaging inflammation. Microglia can be either damaging or protective depending on the context in which they encounter inflammation. Protective microglia promote remyelination and protect axons in MS, thus they are an excellent target for the development of new treatments for MS. However, there are currently no treatments that stimulate microglia to become more protective.
This project focuses on understanding the roles of microRNA, a type of molecular control switch, in influencing microglia to adopt a protective role and thus repair inflammatory damage.
This research will open new avenues to novel therapies that reduce symptoms through promoting remyelination, protecting axons, which will ultimately prevent long term damage and disability in people with MS.
Dr Sarrabeth Stone and her team’s early data has identified microRNAs as candidates for promoting myelin repair, by controlling the function of microglia. Laboratory models showed multiple microRNAs that change how they behave in microglia. These microRNAs are likely to be key in controlling the function of microglia and could be targeted to promote repair of myelin.Â
Dr Stone and her team will be investigating the role of these candidate microRNAs in laboratory models, to work out which of these have the largest effect on microglial function. They will then test the ability of these microRNAs to promote myelination.Â
Walsh, A.D., Stone, S., Freytag, S. Et al. Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system. Commun Biol 6, 555 (2023). https://doi.org/10.1038/s42003-023-04926-8Â
Updated: 31 March 2024Â
$225,000
2022
3 years
Current project
