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 that can support myelin repair in MS and are responsible for regulating 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 are thus 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 at the Florey Institute have made important progress in understanding how microRNAs influence the behaviour of microglia.
Over the past year, the team tested several microRNA candidates in laboratory models to see which could best guide microglia to clear away damaged myelin. This is a crucial first step before new myelin can be formed. Of the candidates studied, one in particular, miR-511, showed strong potential by enhancing this clearance process. This finding highlights miR-511 as a promising target for future therapies.
Additional RNA sequencing also revealed new microRNA candidates that are now being explored in the lab. To help advance this work, Dr Stone’s team is developing a method to deliver microRNAs to the brain using tiny natural carriers called extracellular vesicles, with support from a national expert in this delivery approach.
The project has already led to a published paper and supported two student research theses. A follow-up research paper is in progress, and the next phase of this work is being supported by an MS Australia Project Grant.
This foundational research brings us a step closer to treatments that could repair myelin, protect nerve cells, and slow or prevent disability progression in people with MS.
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/s42003-023-04926-8
Updated 31 March 2025
$225,000
2022
3 years
Current project
