Dr. Ronald Cohn | Sick Kids Hospital, Toronto ON
Dr. Cohn’s laboratory at SickKids has pioneered an approach to successfully treat the underlying cause of Duchenne that is the mutation in the DMD gene. Using the novel gene-editing technology CRISPR/Cas9, they removed large duplications in cells from patients affected by several diseases including multi-exon (18-30) duplication in the DMD gene. Recent progress has been made towards the aim of testing developed treatment in mice. Dr. Cohn’s team generated the first duplication DMD mouse model which specifically mimics a duplication of exons 18-30 (dup18-30) observed in a patient. In a pilot study, they administered their previously described CRISPR/Cas9 gene editing treatment and have observed successful removal of the disease-causing duplication leading to restored full-length dystrophin. Dr. Cohn’s team now plans to further explore the therapeutic window and to design additional strategies to increase the efficiency of their treatment.
Dr. Dongshen Duan | University of Missouri, Columbia MO
Dr. Duan’s team demonstrated effective bodywide systemic AAV microgene therapy in the canine DMD model. Their findings have provided the foundation for the recent initiation of human trials. Through this study, Dr. Duan’s team have developed a novel micro-dystrophin vector for systemic AAV therapy and demonstrated that AAV-8 is more effective than AAV-9 in transducing dog heart for systemic AAV therapy. They have demonstrated for the first time long-term successful systemic AAV micro-dystrophin gene therapy in young adult dystrophic dogs. They have developed a novel non-invasive method to evaluate the overall activity of dogs. They have developed a new physiological assays to study sympatholysis and functional ischemia in dogs.
Dr. Bernard Jasmin | University of Ottawa, Ottawa ON
Dr. Jasmin’s team is focused on repurposing pharmaceuticals that are already approved to treat other diseases to treat Duchenne muscular dystrophy. One promising treatment for Duchenne is aimed at increasing internally-generated levels of utrophin A to compensate functionally for the lack of dystrophin. Recent studies from Dr. Jasmin’s lab revealed that heparin treatment of mdx mice activates a protein (p38 MAPK) leading to an upregulation of utrophin A expression. Based on these findings, the team set out to study the effects of the arthritis medication known as Celebrex in mice with Duchenne. These mice showed improved muscle strength and an increase in utrophin A expression.