Grant: Project Grant

Voluntary movement of muscles in humans requires electric signalling from the nerve cells in the spinal cord to the muscles that help us speak, eat, breathe and walk. This process, called neuromuscular transmission, can be impaired by poisoning, autoimmunity, ageing, and genetic disease. In this research project, I propose to study gene mutations that lead to impaired neuromuscular transmission, so-called congenital myasthenic syndromes (CMS). CMS usually start at birth or early childhood, cause severe muscle weakness, and are often fatal because of respiratory complications. Effective drugs are available to treat CMS, but to select the best drug we need to understand the underlying genetic mutation and its effect on neuromuscular transmission. We currently know about 35 different genes that can cause CMS, many of which were discovered by my research team. However, around 40% of all patients with CMS do not have a genetic diagnosis and available drug therapy is not effective for 50% of patients. The goal of my project is to improve the diagnosis and treatment of CMS; specifically I will: 1. Provide a genetic diagnosis for patients with CMS and discover new CMS genes. I will use genomic sequencing (decoding a person's DNA) to identify gene mutations that cause CMS in a group of 1000 patients with CMS. 2. Understand how gene mutations cause CMS to identify the most appropriate drug or new targets for drugs. I will study the underlying defects in cell and animal models using a variety of scientific techniques. 3. Develop new drug therapies for CMS by testing them in cell and animal models. I will test a variety of drugs in cell and animal models. This research will lead to better diagnosis and therapies for Canadians affected by CMS. Knowledge gained through my research will improve our understanding of neuromuscular transmission disorders.