[Kent Faddis, MU Health System]

Duchenne muscular dystrophy (DMD) is a rapidly progressive muscular disorder that primarily affects males at a rate of approximately 1 in 3500 births worldwide. The disease is caused by a mutation in the dystrophin gene on the X chromosome and is inherited in a genetically recessive fashion. Individuals with DMD have progressive loss of muscle function and weakness, beginning in the lower extremities and sadly leading to premature death.

Within the cells of DMD patients, damaged muscle tissue is replaced with fibrous, fatty, or bony tissue and ultimately loses function. For years, scientists have searched for a way to successfully treat the disorder effectively. Now, researchers from the University of Missouri (MU) have successfully treated dogs with DMD using gene therapy and say that human clinical trials are being planned within the next few years.  

“This is the most common muscle disease in boys, and there is currently no effective therapy,” explained senior author and study leader Dongsheng Duan, Ph.D., professor in the department of molecular microbiology and immunology the MU School of Medicine. “This discovery took our research team more than ten years, but we believe we are on the cusp of having a treatment for the disease.”

The findings from this study were published recently in Human Molecular Genetics through and article entitled “Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus.”

The dystrophin gene mutation within DMD patients disrupts the downstream production of the protein. The absence of the dystrophin protein starts a chain reaction that eventually leads to muscle cell degeneration and death. While the premise of gene therapy for DMD is seemingly straightforward—genetically repair the mutated dystrophin gene—attempts have been hampered by a variety of reasons, the least of which is that the dystrophin gene is one of the largest in the human genome. 

“Due to its size, it is impossible to deliver the entire gene with a gene therapy vector, which is the vehicle that carries the therapeutic gene to the correct site in the body,” Dr. Duan remarked. “Through previous research, we were able to develop a miniature version of this gene called a microgene. This minimized dystrophin protected all muscles in the body of diseased mice.”

Using an adeno-associated virus, the MU team demonstrated that they could deliver the microgene to all muscles in the body of a diseased dog. The dogs were injected with the virus when they were two to three months old and just starting to show signs of DMD. The dogs are now six to seven months old and continue to develop normally.

The dogs Dr. Duan and his team utilized had a body size similar to that of an affected boy. The MU researchers are hopeful that success in the dog will set the foundation for human tests.

“The virus we are using is one of the most common viruses; it is also a virus that produces no symptoms in the human body, making this a safe way to spread the dystrophin gene throughout the body,” noted Dr. Duan. “These dogs develop DMD naturally in a similar manner as humans. It's important to treat DMD early before the disease does a lot of damage as this therapy has the greatest impact at the early stages of life.”

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