Duchenne Muscular Dystrophy (DMD) is the most common genetic muscle disease affecting 1 in 3,500 boys. DMD causes the loss of muscle functions and weakness which usually occurs in children ages 2-6. These children are often wheelchair bound by their teenage years. The life expectancy of an individual diagnosed with DMD is around 20-30 years. DMD is a progressive disease and there is currently no cure.
Dongsheng Duan, PhD at the University of Missouri knows this debilitating disease is caused by a mutation in the largest gene in the genome, the dystrophin gene. Without this gene, the muscle cells die. Dr. Duan’s research focuses on developing gene therapies to fight DMD. “To try and find a therapy is something I really want to do. It’s my dream,” said Dr. Duan. His gene therapy approach will deliver the dystrophin gene back into the diseased muscles. The two main hurdles that he is running into are:
1) the size of the dystrophin gene presents limitations of finding a vehicle that is capable of carrying the entire gene
2) finding the best mechanism to deliver the gene to every essential muscle in the body
His research is focused on creating a micro-gene which will hold the minimal amount needed for a functional dystrophin gene. “We have been trying to work through the gene to find out which part is the essential part that you cannot go without,” he said. The micro-gene is one-third the size of the entire dystrophin gene, but holds all of the essential functions needed for the gene therapy to work.
Dr. Duan first tested this therapy in mice, but he learned that mice do not develop all of the symptoms that humans develop with DMD. A mouse to human scale is not minor so he is researching an intermediate model, the canine model. “Like humans, dogs naturally have the mutations in the gene. We were able to find dogs that have identical symptoms and identical mutations as humans,” said Dr. Duan. He is certain that if a cure is found in dogs with DMD, then there is a high likelihood the therapy will work in an affected child.
To begin with, he injected the micro-gene into a single muscle of affected dogs. “We were able to see fabulous dystrophin restoration and also improvement in the phenotype. We then tested if we can delivery our therapy to every muscle in a diseased dog by a simple intravenous injection. We indeed achieved bodywide muscle gene delivery” he stated. This breakthrough set the stage for onward movement toward gene therapy for humans. “We’re collaborating with several groups, trying to advance this therapy into humans in the next few years and start the first clinical trial,” he indicated. “I believe we have all the skills and technology to be able to make this difference. It’s going to be very meaningful to boys suffering from muscular dystrophy.”
Dr. Duan’s work also involves encouraging and engaging high school students to get involved in science. He invites high school students into his lab to expose them to his scientific research. He has seen some of these students go on to do research in college and even to medical school to study neuromuscular diseases. He believes that engaging with high school students in scientific laboratories and giving them hands-on experience conducting research is the key to inspiring future generations of scientists. “We need to give kids an opportunity to see what real science is. I really support KCALSI’s STEAM (Science, Technology, Engineering, Art, Mathematics) program, we need it and the kids need it.”