In MS, the immune system mistakenly attacks the fatty substance covering nerve cells, called myelin. This triggers inflammation and loss of the protective coating around some nerves. To date, the drugs used to treat MS are mostly immunosuppressive in nature and we are yet to see an effective drug to repair this damage to myelin. There is an urgent need for new drugs to both protect myelin and to promote myelin growth and repair, termed remyelination.
There is a group of drugs used to treat MS called sphingosine-1-phosphate (S1P) receptor agonists, known more commonly as S1Ps, such as fingolimod (Gilenya), siponimod (Mayzent) and the newer addition, ozanimod (Zeposia). These drugs are known to be immunosuppressive in nature, reducing the inflammation commonly seen in MS. However, recent evidence suggests that they may in fact also have properties to promote remyelination. It is also thought that some people living with MS may have low levels of naturally occurring S1P in the body and that these drugs can act like the naturally occurring S1P, potentially explaining some of their positive effects.
Associate Professor Don and his team will investigate if the S1P drugs are myelin protective, if they promote the formation of myelin, and the processes by which this may happen. Additionally, the research team will also explore whether people living with MS may be deficient in the S1P in the first place, helping us to better understand how this class of drug impacts MS. This research will add to our understanding of the mechanisms of action for these drugs, as well as shedding light on a potential source of remyelination for those living with MS.
Associate Professor Don and his team has established that naturally occurring S1P in the body is an important protective molecule for myelin-producing cells and is essential for remyelination following demyelination.
Following this, the team investigated the processes by which this may happen. They have shown that activation of S1P receptors using siponimod, in the absence of naturally occurring S1P, does protect against loss of myelin-producing cells in the face of demyelination. However, siponimod did not appear to rescue remyelination in the absence of naturally occurring SphK2 (the protein that makes S1P in the brain), indicating that a more complex process is involved.
Associate Professor Don and his team plan on learning more about this process, however, the extended lockdown in 2021 meant laboratory work couldn’t take place for a long period of time. They have now tested and established the minimum dose of siponimod needed to protect myelin-producing cells and myelin from demyelination. They will next determine which S1P receptors siponimod mediates its protection through.
Associate Professor Anthony Don was awarded an MS Australia project grant in 2021 to extend this research further.
Updated: 19 January, 2021
Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.
Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.
Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.