Understanding cellular mechanisms

Commencing 2019, A/Prof Simon Murray and Dr Jessica Fletcher, University of Melbourne, were awarded a 2-year Project Grant, fully funded by the Trish MS Research Foundation. The research is investigating promotion of myelin repair in the brain.

Progress in the last calendar year has been limited due to the government enforced COVID-19 lockdown in Victoria. This effectively restricted access to University buildings and services. However, A/Prof Murray and Dr Fletcher were able to gain enough access in order to complete all their animal experiments during the year and begin some analysis of the tissue. These analyses have so far shown that the novel model of demyelination they are using will enable new insights as they observe poor levels of cell survival and myelin repair. This analysis is ongoing, as is the analysis of the effect of their therapeutic candidate.

The histological analyses to examine the efficacy of the remyelinating compound are ongoing. However, earlier studies revealed that a key outcome of the work has been the establishment of a new animal model of MS where the survival and differentiation of oligodendrocytes is impaired, reflective of the current hypothesis of why remyelination fails in MS. A/Prof Murray and Dr Fletcher are making exciting progress on understanding the cellular mechanisms, with clear evidence that repeated short-term demyelination events in this model specifically impacts survival.

Success is being measured by the completion of the studies and the interest received when presented at local and international conferences (being held virtually due to the pandemic), as well as the researchers’ ability to collaborate with additional research groups in validating the next generation of the peptide mimetic that they are using to stimulate remyelination in the current study, and by the interest in this model received from potential industry partners. These are subject to ongoing interactions. The data generated is also being utilised as foundational background work for new NHMRC Ideas grant applications.

There is no change to the research plan detailed in the original application and a no-cost extension from the Trish Foundation was requested and approved in October 2020, the new completion date being October 2021. The histological studies are in progress and A/Prof Murray and Dr Fletcher are optimistic that they will be completed by October 2021.