Multiple Sclerosis (MS) is underpinned by inflammation in the brain and spinal cord. Most treatments aim to stop immune cells like B and T cells from targeting the body’s own tissue. However, these treatments disregard another important arm of the immune system called the innate immune system. This is the body’s first line of defence when viruses or bacteria invade.
This project focuses on two innate cell types, neutrophils and dendritic cells. Neutrophils are the most abundant cell type in human blood and have multiple functions. There are many types of neutrophils but how these relate to MS is unknown. Dendritic cells moderate and direct the effects of B and T cells. There are also different types of dendritic cells, some increasing and others decreasing inflammation.
Using a laboratory model of MS, Associate Professor Anne Bruestle and her team are investigating these different cell populations, their appearance and function in MS. Collaborating with industry partners, Associate Professor Bruestle has developed models to either specifically target innate immune cell types or alter their functions. Associate Professor Bruestle is exploring these for use in MS.
The team will also compare inflammatory and suppressive immune cells in the laboratory model with types of blood cells in people with and without MS. They will see whether there are common factors that could be used as biomarkers (biological signs) for MS activity and potentially for treatment effectiveness. This could also help with developing new treatments, or repurposing treatments for other conditions to find new treatments for people with MS.
Associate Professor Bruestle and her team investigated using neutrophils and dendritic cells as biomarkers of MS activity and as possible new targets for MS treatment. Over the past year, the team established a tool to study the detail of innate immune cells in the blood in MS. The first experiments showed differences in dendritic cells in MS.
The team is also looking at harnessing dendritic cells to help treat MS. One specific type of dendritic cells called “eDCs” increases in the brain and spinal cord as MS symptoms worsen, suggesting that they’re strongly linked to the severity of the disease. eDCs are also good at digesting liposomes. By loading liposomes with an MS drug, they can deliver the drug, via eDCs, to sites of inflammation in the brain and spinal cord. Using liposomes to deliver the drug was up to ten times more effective that using the drug alone in laboratory models of MS. You can read more about this project here.
Over the next year, Associate Professor Bruestle and her team will assess the ability of human dendritic cells (and other immune cells in the same class) to take up liposomes. They will also further investigate dendritic cells in a laboratory model to understand the properties of these cells that might help with better management of MS.
In addition, the team will investigate the impact of neutrophils on the blood brain barrier. This is a protective membrane that separates brain tissue from the bloodstream, but is breached in MS, allowing damaging immune cells into the brain.
Updated 31 March 2025
$650,000
2024
5 years
Current project
