Targeted cell fusion to myofibers: a novel therapeutic approach
Dr. Fabio Rossi, University of British Colombia, Vancouver, BC

Although cell therapy for Duchenne muscular dystrophy shows promise, it has several limitations including a lack of survival of transplanted cells and a lack of cell migration to the desired sites in the body. White blood cells very efficiently migrate to sites of muscle damage, and in rare cases fuse with damaged muscle cells. Following fusion, these cells can “adapt” to their new environment and produce muscle proteins, including a protein called dystrophin that is not produced by the muscle cells of Duchenne patients. However, this cell fusion is very rare and it does not deliver sufficient dystrophin to stop disease progression. If the frequency with which this fusion occurs can be increased, and more dystrophin can be produced, it could result in a new treatment for muscular dystrophies. Dr. Rossi has developed a novel strategy to achieve this goal, which has shown very promising results in the laboratory. The current funding from Jesse's Journey will allow Dr. Rossi and his research team to test this approach in pre-clinical mouse models of Duchenne muscular dystrophy in order to evaluate if it can lead to an improvement in muscle function.

Can the transient inhibition of RAGE signaling improve myoblast survival, proliferation, and migration, and thus increase the success of myoblast transplantation?
Dr. Jacques Tremblay, Laval University, Quebec, QC

Dr. Tremblay's research team has a strong track record working on the development of a treatment for several types of muscular dystrophy based on the intramuscular transplantation of muscle cells called myoblasts. Their animal experiments and recently completed human clinical trials have permitted them to identify some of the problems that limit the success of such transplantation, including a lack of survival of transplanted cells and a lack of cell migration away from the injection site and to other muscles in the body. The current funding from Jesse's Journey will allow Dr. Tremblay and his research group to try and resolve these problems. They hope to do this by blocking a protein called RAGE, which is located on the surface of myoblasts. The binding of RAGE to another protein triggers a signal which leads to myoblast cell death, and this may be contributing to the problems (i.e. poor myoblast survival) seen with myoblast cell therapy. Dr. Tremblay and his research team believe that by transiently blocking RAGE for a few days, they may be able to permit more myoblasts to survive and to migrate away from the injection site, something that will hopefully reduce the number of injections which are currently required to have successful myoblast transplantation.

Diverse strategies to correct dystrophin abnormalities in Duchenne muscular dystrophy
Dr. Jerry Mendell, Columbus Children's Research Institute, Columbus, OH

The goal of Dr. Mendell and his research team is to find an effective treatment for Duchenne muscular dystrophy (DMD) in a timely fashion. DMD is caused by a defect in the dystrophin gene. The product of this gene, a very large protein called dystrophin, protects and stabilizes the membrane. Without dystrophin, the slightest strain or insult to the muscle can cause muscle breakdown. With repeated damage, muscle fibers are lost and the patient becomes very weak. Dr. Mendell and his research team have evidence that gene therapy may be an effective treatment for DMD. They have just completed the first viral gene therapy study ever done on muscle using a modified dystrophin gene. The study has gone well but the method of delivery, by direct muscle injection, in limited in healing capability. Their next goal is to deliver the gene through the circulation so that many muscles can be reached and the patient can benefit clinically. The current funding from Jesse's Journey will help support these studies as part of a larger initiative that includes funding from the National Institutes of Health (NIH) in the United States. In particular, our funding will support studies that are needed in order to get this treatment approved by the FDA as an investigational new drug. Dr. Mendell and his research team know that they are in a race against the clock for many patients, and they will not stop trying until their goal is accomplished.