Supervisor: Toshifumi Yokota
Project: Skipping genes—improving treatment for Duchenne muscular dystrophy by skipping over mutations
Doctor of Medicine
Why did you choose the degree program you are in?
I am passionate about translational bench-to-bedside research and hope to spend my career bridging the gap between academia and industry. I believe that medicine provides a firm understanding of both the physiological and human side of disease, forming a strong foundation for translational research in the future.
What's been the best part of your experience so far?
Meeting and learning from other students in the lab, including a recently graduated PhD student whose defense I had the privilege to watch. It has been fascinating and inspiring to hear about all the research being completed by my peers.
What impact do you hope this project makes once completed? How will this contribute to improving the health of women and/or children?
As a disease affecting children, treatment for Duchenne muscular dystrophy (DMD) would directly improve the quality of life for affected patients and families. We hope that the completion of this project will provide a foundation for future clinical trials and the development of a treatment for DMD.
What's one piece of advice you received from your supervisor/mentor that resonated with you?
After mentioning that progress was delayed with some unexpected experimental setbacks, my supervisor chuckled and simply said, "Yeah, that happens." I am learning that hurdles are inevitable in research, but that overcoming those obstacles is where the majority of learning happens, and can even lead to new research questions and findings.
What has the support from WCHRI, the Stollery Children's Hospital Foundation meant to you?
Support from WCHRI and the Stollery Children's Hospital Foundation has provided me with the opportunity to understand the laboratory science and research underlying the clinical diseases to which I am exposed through my medical education. This deeper understanding will directly improve my ability to care for patients in the long term.
Duchenne muscular dystrophy (DMD) is a lethal genetic disorder affecting children caused by a mutation in a gene known as dystrophin, with an average life expectancy of only 25 years. DMD is characterized by progressive muscle degradation that slowly spreads throughout the body. By the age of 12, most patients are no longer able to walk, and by early adulthood, most patients experience heart and lung issues. While no cure for DMD currently exists, a growing class of DNA-like molecules known as morpholinos have shown promise in treating DMD by "skipping over" the mutated region of gene transcripts, helping to improve patient's quality of life and increase their lifespan. Current morpholinos on the market suffer from limited scope and can only treat eight to 13 per cent of DMD patients.
In this proposal, we aim to address this limitation by testing a combination of morpholinos known as a “cocktail” designed to skip multiple sections of the gene at once, which will increase the number of patients who are able to use this treatment. Specifically, we aim to skip exons 45-55, a range that can treat approximately 50 per cent of DMD. The cocktail treatment will be tested in an animal model harbouring the human DMD gene, and efficacy will be determined by evaluating behaviour, cardiac phenotype, or observable traits, and gene expression analysis. This work will lay the foundation for future clinical trials. Overall, this research will support a shift towards improved quality of life for DMD patients by aiding in the development of a better treatment that is applicable to more patients.