Defining a dual role for VGF in the regulation of MS pathology
Principal Investigator: Dr. David Picketts
Affiliation: Ottawa Hospital Research Institute
Year awarded: 2018-2019
Amount Awarded: $312,528
Keywords: VGF, macrophage/microglia, inflammation, oligodendrocytes
- VGF is a molecule that is induced during exercise and is shown to increase myelination. VGF also promotes the maturation of myelin-producing cells called oligodendrocytes.
- VGF interacts with macrophages/microglia- immune cells that can be both detrimental and beneficial in multiple sclerosis (MS). VGF is believed to promote the reparative functions of macrophages/microglia but how remains unknown.
- The research team will:
- Determine the molecular players involved in regulating the beneficial effects exhibited by VGF in MS
- Determine how VGF promotes maturation of oligodendrocytes
- Examine the reparative role of VGF molecules in an animal model of MS
We know that exercise can alleviate many symptoms associated with MS, and in some cases, slow disease progression. Precisely why is somewhat of a mystery. Previous research led by Dr. David Picketts identified one possibility – a small molecule called VGF. Produced in the brain during exercise, VGF supports the growth of myelin-producing cells, making it an excellent target for treatment. Furthermore, VGF interacts with macrophages—an immune cell that has a dual function: sends signals to attract T cells and promote inflammation in MS and also promote repair by recruiting myelin-producing cells (oligodendrocytes) to the lesion site. Dr. David Picketts believes VGF functions through activating signals on macrophages that promote repair. To test this theory, the research team will examine the molecular pathways through which VGF is involved in tipping the balance of macrophages from their detrimental role to a beneficial one. The research team will also test drugs regulating VGF in mediating repair in a mouse model of MS. This research will produce a thorough understanding of molecular pathways involved in repair in MS, and how VGF influences them, while also determining the importance and potential of VGF as a therapeutic molecule.
Potential Impact: VGF compounds that signal to macrophages to promote repair could potentially be novel therapeutic for MS.
Project Status: In Progress