A New Mouse Model Linking Degeneration with Inflammation to study Multiple Sclerosis
Year Awarded: 2019
Term: 3 years
Funding Amount: $345,000
Affiliation(s): University of Calgary
Researcher(s): Dr. Peter Stys
Impact Goal(s): Understand and Halt Disease Progression
Summary: This research aims to explore how MS is initiated and hypothesizes that MS starts as a degenerative disorder and then leads to an aggressive autoimmune attack against nerve fibers in the brain resulting in inflammatory ‘plaque’. To test this hypothesis, the group has developed a new animal model of MS and will use this model to study the biological details of the autoimmune reaction.
Project Description: There is ongoing vigorous debate in the field about how MS is initiated. This research aims to study whether MS is a primary defect of the immune system cells (T cells) driving autoimmune inflammatory damage of nerve fibers (i.e., demyelination), or if an underlying degeneration pre-dates the autoimmune response. This project introduces a new mouse model of MS termed ‘Cuprizone Autoimmune Encephalitis’(CAE). This model starts with a degenerative biochemical injury to myelin (the outer insulation of nerve fibers) in the brains of mice, similar to what is thought to occur in humans years or possibly decades before the first clinical MS attack. The CAE model can be used to understand how “biochemical dysmyelination” drives inflammatory effects similar to what is seen in later stages of MS. The CAE model may represent a new realistic animal model of MS.
Potential Impact: This CAE model may represent a new realistic animal model of human MS, allowing the detailed study of the interaction between two key components of this disease: biochemical injury to myelin (the outer coating of nerve fibers), and the resulting inflammatory reaction that adds fuel to the fire. Ultimately, CAE could be an ideal model in which to test new drugs that are effective for both inflammatory relapses and the underlying degeneration, which together produce the disability commonly seen in progressive MS.
Project Status: In progress