Clearance of myelin debris

An Incubator Grant titled, “TREM2 and clearance of myelin debris in MS” was awarded to Associate Professor Michael Buckland, following very generous support of donors at our Trish MS Winter Wonderland Ball.

Multiple sclerosis (MS) is a disease in which the immune system attacks a protective sheath, called myelin, which covers nerves in the central nervous system (CNS-brain and spinal cord). Myelin damage is referred as demyelination and the consequence is the disruption of communication between the brain and the rest of the body. The CNS has the potential to generate new myelin (process named remyelination) after damage, but for unknown reasons remyelination fails or is incomplete in MS. Efficient removal of myelin debris is a necessary prerequisite to remyelination. In the CNS a specific cell type, called microglia is capable of clearing out myelin debris after damage. In MS lesions, microglial cells are activated and one of their functions is to pick up and digest myelin debris (process called phagocytosis). The mechanisms mediating microglia activation and phagocytosis are not known.

In this regard, A/Prof Buckland has been studying the role of triggering receptor expressed on myeloid cells 2 (TREM2), a molecule expressed on microglia membranes. As part of the grant funded by the Trish MS Research Foundation, A/Prof Buckland and his team have demonstrated that TREM2 is highly expressed on microglia cells which are active in ‘eating up” myelin debris. Furthermore, using an animal model of demyelination they have shown that activation of the TREM2 receptor led to more efficient clearance of myelin debris by microglia and promoted remyelination. This could be relevant as a possible strategy to facilitate the removal of damaged myelin from the tissue and thus potentially enhance remyelination in people with MS. A/Prof Buckland and his team are continuing their research into how TREM2 promotes myelin clearance with the ultimate aim of informing intelligent drug design to accelerate lesion repair in MS.

This pilot proposal will allow generation of preliminary data that will be used to apply for larger research grants to MS Research Australia and the NHMRC.