Grant: Foundation Grant

<html> <body> <p> <strong>Overarching direction</strong><strong>of research program</strong> <br> The neuromuscular diseases (NMDs) include more than 140 different conditions that involve weakness of muscles and/or numbness caused by muscle and nerve illness. Most NMDs are incurable. In recent years, promising preclinical studies have motivated new therapeutic approaches for NMDs. However, many barriers remain in the translation of research into therapeutics.<br> <em>My</em> <em>overarching</em> <em>research program goal is to discover, optimize, and translate novel therapies for NMDs.</em>Antisense-mediated therapy is an exciting new approach to treat NMDs. Antisense therapy uses short DNA-like molecules that act like a stitch to modulate gene expression and RNA splicing. My research team has demonstrated the first systemic treatment using antisense therapy in mouse and dog models of Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder worldwide, and has led to Phase III clinical trials.<br> <br> <strong>Approach</strong> <br> <em>We will</em> <em>develop innovative and safe therapies for the treatment of neuromuscular diseases</em>. Specifically, we will: 1) design effective antisense-mediated therapies by <em>in silico</em> analysis 2) develop and characterize novel <em>in vivo</em> disease models that appropriately recapitulate human NMDs, 3) measure the efficacy and safety of antisense therapies in cell and animal models; and 4) translate this knowledge into clinical practice through the Canadian Neuromuscular Diseases Network (CAN-NMD) and international collaborations. This vision incorporates multiple research modalities, including bioinformatics, efficacy analysis of antisense drugs with cell transfection methods, and <em>in vivo</em> systemicanimal trials. While our work on DMD is in preclinical stages in large animal models, we are at various stages of cell/mouse models for three other NMDs in which RNA-mediated therapies are predicted to be effective. My interdisciplinary research will maintain a focus on translation into therapeutics, leading to clinical trials in people with NMDs.<br> <br> <strong>Core</strong> <strong>expertise</strong> <br> I have received international recognition for my expertise in antisense therapy for muscular dystrophy and neuromuscular diseases. Over the past 15 years, my work has provided <u>roadmaps for</u> <u>clinical trials</u> including three independent Phase II/III clinical trials using antisense therapy for DMD. I established my research laboratory at the University of Alberta in 2011. Since then, I have published 15 articles (8 as corresponding author) in prestigious journals such as <strong><em>Nature, PNAS, Hum Mol Genet,</em></strong> and<strong><em>Mol Ther</em></strong> (3 papers). I currently hold the Muscular Dystrophy Canada (MDC) Research Chair, and am a member of the Scientific Advisory Boards for MDC and for the Patients' Association for Dysferlinopathy Japan.<br> <br> <strong>Training and mentoring</strong> <br> The collaborative and multidisciplinary approach of my research program supports my trainees in developing skills essential to translational research. I have many ongoing collaboration programs with industries, and am currently a Principal Investigator for three government-funded collaborative programs: 1) CAN-NMD, a pan-Canadian network of researchers, clinicians, and patients focussed on NMDs (CIHR-funded); 2) SKIP-DMD, an international exon skipping network of researchers developing new generation antisense drugs (CIHR-funded); and 3) DMD-pig, the development of a transgenic pig model of DMD (NIH-funded). My research program is expected to help trainees learn skills in translational research, communication, and teamwork project management.</p> </body> </html>