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MS is a disease resulting from damage to the insulating substance around nerve fibres in the brain and spinal cord, called myelin. It occurs when the body’s own immune system mistakenly identifies myelin as a foreign invader. MS most commonly presents with a relapsing-remitting (RRMS) disease course, which is categorised by flare-ups followed by periods of recovery. However, many people with RRMS end up developing secondary progressive MS (SPMS), which is categorised by a steady worsening of symptoms without recovery. A minority of people present with primary progressive MS (PPMS), where there is a steady accumulation of disability right from diagnosis.
While many treatments are now available for RRMS, there are few effective therapies for progressive MS that prevent the worsening of disability. This may be because there are different biological processes involved in relapsing and progressive MS. Current therapies generally target cells in the immune system that are thought to directly attack nerve cells. However, a potentially more potent approach is to dampen down the initial stimulation of the immune system. This could be done by having a treatment that mimics the natural signals that dampen down immune responses.
Existing work from this laboratory group has identified some of these signals. They have also found a gene involved in regulating the immune response, found in 40% of Caucasian people with MS, which can increase the likelihood of developing progressive MS.
The aim of this project is to study ways to dampen down the abnormal immune activation in MS, which will hopefully lead to new ways of combatting MS.
Dr. Vivien Li’s research has made significant progress in developing a therapy for MS using immune cells from blood of people with MS. The goal is to modify these cells in the lab to selectively target and suppress the disease-causing immune cells that promote inflammation and nerve damage in MS.Â
Dr Li and her team have successfully isolated immune cells and generated special tissue cells called dendritic cells (DCs) from them. They have refined the cell culture conditions to promote the development of DCs with anti-inflammatory characteristics. One important factor in this process is the use of dexamethasone, which reduces the level of proteins and chemical signals that activate the immune system.Â
By designing peptides (a short string of amino acids) derived from a protein called RASGRP2, which is associated with MS, the team has identified specific peptides that can activate the immune system. They have also shown that dexamethasone can modify the immune response to these peptides. When these peptides were added to immune cells from people living with MS, the cells released inflammatory signals, indicating their reactivity to the peptides.Â
Furthermore, the team used specialised techniques to identify immune cells that specifically recognise the RASGRP2 peptides. These cells were found to be higher in number in the blood of people living with MS compared to people living without MS, highlighting the significance of these peptides in MS biology.Â
Dr. Li’s research lays the foundation for developing future therapies that promote immune tolerance and potentially alleviate the symptoms of MS.Â
Updated: 31 March 2023
Dr Vivien Li
$30,000
2020
3 years
Past project
