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A number of important biological processes contribute to disease in MS, including inflammation and neurodegeneration (nerve loss). While inflammation is reasonably well understood and treatable with current drugs, neurodegeneration is more complex, poorly understood and only responds to treatments in a very limited manner. Neurodegeneration is also thought to underlie progression of MS. The burning question, therefore, is: what is the cause of nerve loss?
Recent scientific evidence shows that blood particles known as ‘platelets’ play an important role in autoimmune diseases such as MS. Platelets are small cell fragments that are important in blood clotting, but also have wider functions, including the capacity to exacerbate inflammation in laboratory models of MS.
Dr Orian’s research has shown that the role of platelets goes even further and that these particles are key drivers of the autoimmune process and might be responsible for both inflammation and neurodegeneration. She suspects that platelets, rather than immune cells, cause nerve loss and that targeting platelets in early disease may slow down some of the degeneration of nerves in MS, thereby potentially delaying progressive MS.
The overarching aim of this project is to demonstrate that platelet-targeting is both anti-inflammatory and neuroprotective in MS, using a novel platelet-targeting drug. This will provide proof-of-concept for the potential of platelet-targeting therapies to treat MS.
Dr Orian has made significant progress to date. As part of the project, Dr Orian and her team have developed a laboratory model that more accurately represents MS. Current models exhibit aggressive disease and rapid progression and are also not feasible for treatment evaluation. This newly developed model exhibits less aggressive disease, enabling treatment evaluation. Dr Orian and her team have confirmed that the model experiences inflammation and have identified the earliest evidence of platelet infiltration into the brain and spinal cord.
Dr Orian’s preliminary work in laboratory models of MS has demonstrated that platelets are associated with cells of the brain and that proinflammatory molecules were detected around nerve cells. Further laboratory work has shown that nerve cell death occurs when grown in the presence of platelets. In the absence of platelets, nerve cells continue to grow and multiply.
Using a novel drug (scFvCD39) which specifically blocks disease-associated platelets, Dr Orian and her team demonstrated in the laboratory models of MS that this drug stopped disease progression and provided protection from neurodegeneration. Unexpectedly, they also found that the drug promoted remyelination. This was associated with restoration of mobility.
This work provides exciting proof-of-concept for the potential of platelet-targeting therapies to treat MS. While these early results are promising, there is a long path to take this drug from the lab to the clinic. It is our hope that such therapies will one day have a significant impact on the lives of people with MS.
Updated: 31 March 2022
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.
$240,000
3 years
