Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease, caused by a genetic mutation that prevents the body from producing vital SMN protein. Without adequate SMN protein, motor neurons in the spinal cord die. Without motor neurons, the brain and spinal cord are unable to communicate with muscles, leading to weakness, paralysis and early death. While current therapies are able to improve strength and extend lifespan in many patients, some patients respond well to therapy while others do not. Even for those who respond well, treatment is only partially curative, and for this reason research must continue to explore new therapies and new combinations of therapies to better treat this debilitating disease. Our lab is currently exploring the effects of a new genetic therapy that may boost SMN protein levels and provide a permanent fix for patients with SMA. We are testing this therapy using mice that have been engineered to have SMA. We are also exploring the effect of combining our new genetic therapy with two currently approved treatments to see if either combination can further increase SMN levels, prevent muscle weakness and restore mobility in our mice. To evaluate the effect of our combination therapies, we treat the mice on their first day of life and after 2 weeks, measure the level of SMN protein in different tissues. Using a microscope, we count the number of motor neurons in the spinal cord to see if any have died and if they appear large and healthy. We look at how well connected the motor neurons are to muscle tissue, record if any connections are broken and look for other signs of disease. We measure the size of muscle fibers and look for signs of poor muscle development. Similar to in humans, we also assess walking ability in our mice and conduct a series of coordination tests. Through analysis of this data we can determine how well our therapies prevent the onset of SMA and if either combination of therapies should be further studied.