In January 2020, Professor Trevor Kilpatrick, Florey Institute of Neuroscience and Mental Health, was awarded a 3-year Trish Translational Research Project Grant titled, “Dendritic cell therapy for multiple sclerosis”.
Most current treatments for MS broadly suppress the immune system, but this can increase risks of infections and cancers. A more targeted approach is to dampen down immune cells specifically involved in attacking the nervous system. This could be achieved by giving the immune system an inhibitory signal in a targeted way. We have adopted both preclinical and clinical approaches to study this.
In the preclinical work, we aimed to determine if the ablation of an immune modulating molecule known as MERTK changes the activation profile of the immune cells responsible for producing tissue damage in autoimmune conditions like MS. Our work indicates this is not the case but leaves open the possibility that medication related activation of the MERTK protein could still have therapeutic potential.
In the human work, we have collected blood samples from controls and people with MS to test for the beneficial effects that activation of the MERTK gene might induce. From these samples, we have developed and verified techniques to isolate, purify and grow the immune cells responsible for stimulating the attack cells. In particular, we have assessed for expression of characteristic cell surface markers on these cells which, when activated, have important functions in suppressing the immune system. We have also been investigating the types of MS-associated proteins that are taken up by these immune cells and presented on their surface to initiate the immune responses responsible for causing damage. By identifying these proteins and combining them with the signals that otherwise suppress the immune system, we aim to turn off the abnormal immune activation specific to nerve cells in MS, whilst leaving the immune system still able to respond to other infections and insults.
Professor Kilpatrick and his team have collaborated with Monash University. Some experiments have been performed at the Immunoproteomics Laboratory, Monash University, led by Professor Anthony Purcell.