Grant: Doctoral Research Award: Canada Graduate Scholarships

Canada has among the highest rates of multiple sclerosis (MS) in the world and studies suggest rates may be highest in Saskatchewan. In progressive MS, the nerve cells of the brain and spinal cord are damaged in a process called neurodegeneration, a well-known feature of MS. Many researchers believe this is the reason why people living with MS get worse. The cause of this nerve damage is unknown and treatments that halt or prevent it are currently unavailable. Our team discovered that autoantibodies, molecules made by the body that attack itself, to a specific nerve cell protein called 'heterogeneous nuclear ribonucleoprotein A1' (or 'A1' for short) may lead to neurodegeneration in people living with MS. In healthy individuals, 'A1' performs a number of functions to help cells stay alive. However, in people with MS, 'A1' becomes misplaced within the nerve cell leading to its malfunction and damage to the brain and spinal cord. We have shown that the addition of 'A1' autoantibodies (similar to those found in people with MS) to mice with MS-like symptoms makes the mice sicker. Additionally, giving 'A1' autoantibodies to these mice leads to 'A1' malfunction and significantly increased death and damage to nerve cells compared to mice injected with non-specific antibodies, which do not enter nerve cells. The next step is to test treatments that minimalize the harmful effects of 'A1' autoantibodies on nerve cells. This work suggests a new theory about how nerve cells are damaged in MS. By understanding how 'A1' autoantibodies and 'A1' malfunction cause nerve cell damage or death, we will be able to design new medications to treat neurodegeneration in MS, reduce the disability associated with neurodegeneration and improve the lives of persons living with MS.