VUB professor Kiavash Movahedi, affiliated with the Vrije Universiteit Brussel Faculty of Medicine and Department of Biomedical Sciences, has won an ERC Consolidator Grant for his research on microglia. Microglia are highly versatile brain cells that have enormous therapeutic potential. They are critical for maintaining healthy brain physiology. Movahedi wants to use the €2 million grant from the European Research Council to develop a therapy in which he can replace malfunctioning microglia in the brain with genetically modified counterparts, which have better function. Those transplanted microglia could then play an important role in preventing or curing a range of neurodegenerative diseases, such as Alzheimer’s or frontotemporal dementia.
Microglia are non-neuronal cells that are active in the brain. They are actually the brain’s immune cells that play an important role in supporting neurons. “We are increasingly realising that malfunctioning microglia can be associated with a wide range of neurological disorders, making these cells an important target for therapeutic intervention,” says Movahedi. “Microglia are very special cells: they are enormously versatile and involved in a lot of essential processes. Surprisingly, almost all microglia are made from precursors that already form in the yolk sac of an embryo. These embryonic precursors infiltrate the brain very early during embryonic development, turn into microglia there, and can then sustain themselves for life. This is quite unique, as most other immune cells need to be continuously replaced by stem cells from the bone marrow. Their amazing ability to self-renew presents a unique opportunity for cell therapy. The ability to replace dysfunctional microglia with healthy or genetically improved counterparts could completely change the way we treat brain diseases.”
The question, however, is how to replace microglia and how to enhance or extend their positive functions. “Microglia are very adept at self-renewal,” says Movahedi, “so being able to replace them is quite a challenge. One of the difficulties is to put on hold the microglia present in brains. Their regenerative capacity is so great that even if we eliminate 99% of the microglia present in the brain, after only a few days their numbers are back to normal. We therefore need to shut down that natural regeneration of the brain microglia, so that our transplanted precursors can take over. There is also the question: where do we get the cells we use to replace microglia? We are working on technologies that allow us to turn skin or blood cells back into stem cells, which we then turn into precursor cells capable of turning into microglia in the brain. A final challenge is to develop genetic strategies that allow us to make these new microglia fitter and more useful than the original cells, thus preventing the deterioration of neurons in the brain.”
By building on their expertise and unpublished observations and developing innovative technologies, Movahedi and his team aim to lay the groundwork for a new form of cell therapy. Their microglial replacement therapy has the potential to result in a new and long-awaited breakthrough in the treatment of neurodegenerative brain diseases.