Grant: Project Grant

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease. As people living with MS become older, a majority of them will develop progressive MS by middle-age. Progressive MS causes chronic brain damage which leads to irreversible disabilities. There are currently no effective treatments for progressive MS, in part because we do not fully understand what causes chronic brain damage. As Canada has the highest prevalence of MS in the world and with an aging population, determining what promotes MS progression and identifying effective treatments for progressive MS are urgent unmet health care needs. Chronic brain damage in progressive MS associates with oxidative stress. Oxidized phosphatidylcholines (OxPC) are byproducts of oxidative stress which are increased in acute and chronic MS brain lesions. Yet, how OxPC contribute to chronic damage in the brain and spinal cord during progressive MS remain mostly unknown and needs urgent investigation. In this proposed project, we aim to determine how OxPC propagate inflammation and chronic injury in the brain and spinal cord white matter and grey matter. Specifically, we will use middle-aged male and female mice to study how OxPC mediate chronic brain and spinal cord damage. We will then use neuronal cell cultures to determine how different types of central nervous system cells respond to OxPC induced stress. We will also validate key discoveries in chronic brain lesions from progressive MS brain tissue specimens. Finally, we will evaluate the effectiveness of neutralizing OxPC as a therapeutic approach to slow or halt chronic brain and spinal cord damage in both young and middle-aged mice. Together, we will advance our knowledge in the mechanisms that underly MS progression and we will make discoveries towards protective therapies for progressive MS.