Grant: Doctoral Research Award: Canada Graduate Scholarships

GNE myopathy is a rare inherited neuromuscular disorder which presents in early adulthood with progressive leg weakness leading to loss of ambulation and severe disability. The disease is estimated to affect between 1 and 9 in 1,000,000 individuals, however, the exact prevalence is unknown as many patients remain undiagnosed. The causative gene in GNE myopathy, GNE, is responsible for the synthesis of sialic acid. It is thought that GNE myopathy is the result of reduced production of sialic acid, however, a phase 3 human clinical trial showed no improvement with sialic acid treatment. Despite these results, it is still believed that sialic acid plays a role in GNE myopathy. Recent evidence suggests that proteins linked to long chains of sialic acid may be implicated in the disease. So far, only a handful of these proteins have been identified in humans including one called neural cell adhesion molecule (NCAM), which plays a role in the regeneration of muscle following injury and with age. In addition to sialic acid, other pathways have also been found to be dysregulated in previous GNE myopathy research. This project aims first to estimate the overall prevalence of GNE myopathy using data obtained from numerous genomic databases. We also propose investigating the role of proteins linked to long sialic acid chains as well as other key cellular pathways in GNE myopathy to uncover the likely mechanism of disease. Finally, we will test new drugs in our GNE myopathy models to determine if they can correct any of the observed defects in sialic acid and/or the cellular pathways of interest. This work will improve the understanding of the epidemiology and pathophysiology of GNE myopathy and support the advancement of drug development and clinical trials.