Grant: CIHR Fellowship

Multiple sclerosis is a neurological disease affecting 2.8M individuals worldwide (Atlas of MS, 2020). Most MS patients will eventually suffer from the progressive form of the disease (PMS), characterized by irreversible progression of disability. There are currently very few treatment options for PMS and they are all limited in efficacy. Our lab has previously demonstrated that astrocytes and microglia, two types of brain-resident cells, contribute to the progression of MS by undergoing a specific biochemical reaction called sphingolipid metabolism. We have also identified the FDA-approved Miglustat as a potential therapy for PMS due to its capacity to suppress this pathogenic reaction. The goal of my research project is to repurpose the FDA-approved Miglustat as a novel and effective treatment for PMS. To achieve this goal, we first propose to test the impact of Miglustat on the pathogenic activities of astrocytes and micrglia by performing a battery of experiments in highly controlled settings on brain cells isolated from discarded surgical human specimens and research animals. Subsequently, we aim to investigate the therapeutic effect of Miglustat pre-clinically, that is in research mice with a disease reminiscent of PMS. More precisely, we will administrate Miglustat into these animals in different doses and measure its impact on disease progression by evaluating each of them on a daily basis. Because of the urgent unmet need to establish novel therapies for PMS, the success of our project will result in a significant impact on the lives of patients with PMS. In other words, it will establish Miglustat, an FDA-approved therapy that is safe for use in humans, as a promising novel treatment for PMS ready for clinical testing.