Hierarchy of Inhibitors in the Lesion Microenvironment for Remyelination: Combining a Novel CNS-Targeting Therapeutic with Exercise to Promote Repair
Year Awarded: 2019
Term: 3 years
Funding Amount: $415,613
Affiliation(s): University of Calgary
Researcher(s): Dr. Wee Yong
Research Priorities: Repair/Remyelination
Impact Goal(s): Understand and Halt Disease Progression
Summary: MS results from abnormal activity of the immune system whereby the body’s own immune cells target and damage myelin (the outer protective coating of nerve fibers) and myelin-producing cells called oligodendrocytes located in the central nervous system. Regeneration of oligodendrocytes and subsequent repair of myelin is believe to occur in brain lesions of people with multiple sclerosis (MS). With this knowledge, research and clinical trials now in progress seek to enhance the repair of myelin (remyelination) in people with MS. Several inhibitors have been identified, which can be thought of as ‘brakes’ to remyelination, raising the question of whether there is a relative potency of these inhibitors as impediments to repair. This study will test the hypothesis that there is a hierarchy of the importance of these inhibitors (or brakes) and examine their relative potency.
Project Description: Remyelination occurs in MS in spite of inhibitors deposited in lesions. These brakes, including chondroitin sulfate proteoglycan (CSPGs) and LINGO-1, have been independently studied and therefore their relative importance is unknown. Through this work, Dr. Wee Yong and team will test the hypothesis that there is a hierarchy of inhibitors with CSPGs being predominant. They will simultaneously evaluate the expression and properties of several inhibitors, using models and MS samples. They will also evaluate the impact of exercise, which has been shown to increase remyelination, in combination with a CNS-targeted novel medication that reduces CSPG production, in overcoming inhibitors. This study should help define the critical molecule that must be overcome in order to foster repair in MS.
Potential Impact: This study is important to the growing field of repair and regeneration strategies for MS, as they seek to understand and overcome the impediments (or brakes) to remyelination and regeneration.
Project Status: In progress