Multiple Sclerosis is an inflammatory demyelinating disorder of the brain caused by an immune system attack on myelin and/or the cells that produce myelin (oligodendrocytes) and support neurons. This leads to a widespread loss of neuronal function and deficits in executive and cognitive functions, which result in a major loss of quality of life and independence for the 2.3 million people with MS worldwide. Moreover, MS pathology is a self-perpetuating deleterious cycle of neuroinflammation and neurodegeneration that leads to neuronal loss. Over time, individuals commonly enter a protracted, chronic degenerative phase of the disease, known as progressive multiple sclerosis (PMS). Two anti-inflammatory treatments, ocreluzimab and siponimod, have recently been approved for the treatment of PMS, but less than half of individuals with PMS are suitable for these therapies. Moreover, systemic medical treatment such as these is limited by the inability of drugs to cross the blood-brain barrier. The particular issues being addressed by this project are an incomplete understanding of the molecular underpinnings of disease course and pathology and the sub-optimal management of the disease course. An improved understanding of the biological changes occurring in the immune and central nervous systems should help to identify novel targets for MS therapy, improve drug delivery platforms and increase the proportion of individuals that receive and are responsive to disease-modifying therapies. This is important for society as a whole, as successful MS therapies enable those living with MS to be employed for longer, placing less of a burden on healthcare systems the other family members. The overall objectives of the research carried out by members of the PMSMatTrain consortium were to do the following: 1) develop improved lab-based and pre-clinical models of MS pathology; 2) use these models to test candidate drugs that inhibit inflammation and promote the repair of damaged nerves; 3) design a novel, minimally-invasive device that targets in particular, disease in the outer layers of the brain (the cortex); 4) facilitate slow, long-term release of drugs from the device, using ‘tuneable’ bio-based hydrogels.
