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In people with MS, the insulating, protective layer around nerves known as myelin, is attacked by the immune system. Although myelin can be repaired, individuals with MS experience a loss of myelin repair capacity in certain cells called oligodendrocyte progenitor cells (OPCs), and the exact cause of this impairment is not fully understood.
It has recently been discovered that OPCs play a role in shaping connections between brain cells, in addition to producing myelin. They achieve this by a process called phagocytosis, which involves ‘eating’ the connection points (synapses) between nerve cells to ensure proper nerve connections. However, it is possible that OPCs engaged in phagocytosis may not be able to generate myelin and contribute to repair in MS.
Dr Natalie King and her team are investigating whether OPCs that undergo phagocytosis can still produce myelin. Additionally, they aim to determine if (low-density lipoprotein receptor-related protein 1 (LRP1)), a specific molecule on OPCs, can influence their ability to engage in phagocytosis. By unravelling these mechanisms, they hope to uncover the factors that hinder myelin repair in MS and find new ways to guide OPCs towards generating myelin, thus promoting brain repair in individuals with MS.
Since the initial stages of the research, Dr Natalie King and her team have made significant progress. They have successfully completed key experiments to investigate whether OPCs that engage in phagocytosis can still contribute to myelin repair in MS. Their findings suggest that while OPCs consume both synapses and myelin, this process impacts their ability to differentiate and form new myelin, potentially reducing their contribution to repair.
In the past year, the team has established that OPCs in the brain’s hippocampus, a region linked to memory, also undergo phagocytosis, adding complexity to their role in brain function. This discovery is especially important as synapse loss in the hippocampus can contribute to cognitive issues like memory disturbances, which are common in people with MS.
Additionally, the team explored the role of LRP1 in OPC phagocytosis and its potential impact on their myelinating abilities. While final analyses are ongoing, the research has already generated promising insights into how OPCs interact with brain synapses and myelin. These findings are guiding the team in developing new strategies to drive OPCs towards myelin production, which could improve brain repair mechanisms in people with MS.
In addition to the funding from MS Australia, Dr King and her team were awarded an additional $20,000 through the 2023 Menzies Peer Support Innovation Award Scheme. This extra funding has allowed the team to further expand their research, support student training, and initiate new studies that advance the understanding of OPC behaviour in MS. Several publications are now in preparation based on this work, with one expected to be published shortly.
Updated 31 July 2024
$24,565
2023
1 year
Current project
