Grant: Foundation Grant

Voluntary movement of muscles in humans requires electric signalling down the nerves: beginning at the spinal cord and ending at muscles that help us speak, eat, breathe and move. This process is impaired in neuromuscular diseases (NMDs), which are associated with progressive muscle weakness, disability and early death. Until recently, most NMDs were very difficult to diagnose and considered untreatable. Fortunately, genomics (deciphering a person's genetic code to understand the mutation responsible for a particular disease) has transformed our ability to diagnose and treat these devastating disorders. My research program studies gene mutations responsible for NMDs to provide a diagnosis, understand disease progression, and test new therapies. My program focuses on two types of NMDs: congenital myasthenia syndromes (CMS) and myotonic dystrophy (DM1). I will use a combination of genomics, molecular biology, animal models, and clinical trials to improve their diagnosis and treatment. Specifically, I will: 1.Use genomics to identify the genetic causes of CMS while discovering new disease genes. I will provide a genetic diagnosis for at least 300 families with CMS while discovering at least 20 novel genes. 2.Use genomics, molecular biology, and animal models to understand how genetic mutations cause NMD in order to guide treatment and identify new therapies. I will reveal the genetic mechanisms of 20 new NMD genes, discover 5 new therapies, and study 7 therapies (4 re-purposed, 3 new) in animal models. 3.Build an 'Ottawa River' cohort of 250 families with DM1 and use patient samples to study biomarkers. I will identify 10 biomarkers to indicate which patients will be most responsive to therapy and another 5 to measure treatment response in clinical trials. 4.Conduct clinical trials to test new NMD therapies for CMS and DM1 using novel and repurposed drugs. This research will improve the diagnosis and treatment of NMDs and grow Canada's international leadership.