Recipient: Associate Prof Anthony White
Boosting microglia phagocytosis as a therapeutic approach to treat MND.
Funding from MND and Me is supporting our team to further understand how the immune system in the brain and spinal cord is impaired in MND. In particular we have found that microglia (the brain’s specialized immune cell) are impaired in people with MND. An important function of microglia is phagocytosis which is when the cell engulfs and breaks down unwanted waste material in the brain (like lots of small rubbish trucks). Our research has shown that this ability is failing in microglia from people with ALS and this could be making the disease worse. We are therefore trying to understand how this is happening, and how we can repair the problem. We have developed an interesting potential therapeutic approach that can restore normal phagocytosis in the microglia in the test tube. We are now trying to work out which are the right people with ALS who will benefit from a treatment based on this approach. This is needed as microglia can behave quite differently from one person to the next depending on what type of ALS they have. As a consequence, we are trying to personalize the treatment.
We are also developing a model system that allows us to look at how microglia respond to potential drugs in 3D. Cells are normally grown in the lab in 2D on flat petri dishes, but this can change the way microglia behave as they normally exist in a complex 3D environment in the brain and spinal cord. We are finding, as expected, that microglia grown in 3D show different patterns of behaviour to those grown in 2D. Therefore, if we can show that a drug can repair a process like phagocytosis when the cells are grown in 3D, we believe that the drug will have a greater chance of working in clinical settings. Our team is very grateful for the support of MND and Me and MNDRA to allow this important research to be undertaken.