Gene therapy treats muscular dystrophy in dogs

The researchers demonstrated safe and efficient systemic gene delivery for the first time in large mammals with muscular dystrophy, but many significant obstacles remain. morningmagenta/iStock/Thinkstock

Muscular dystrophy is a group of more than 30 genetic conditions that break down the muscles that control body movement and heart contraction. The most common type is Duchenne muscular dystrophy (DMD), which primarily affects boys.

DMD is caused by mutations in the gene for dystrophin, a protein crucial for muscle cell structure. Without dystrophin, muscle cells develop properly but gradually become damaged and die over time. Muscles progressively weaken, usually beginning before age 6. People with the disease are now surviving into their 30’s and beyond due to advances in the management of breathing and heart complications.

Since DMD results from errors in a single gene, scientists have been trying for years to use gene therapy to treat the disease. Unfortunately, they’ve faced many challenges. The dystrophin gene is one of the largest known, so it’s impossible to deliver an entire working version of the gene inside a harmless virus, or vector. The therapy also needs to treat all the muscles throughout the body, rather than just a single organ. 

A team led by Dr. Dongsheng Duan from the University of Missouri School of Medicine has been working on DMD gene therapy for years. The group had previously developed a miniature version of the dystrophin gene, known as a microgene, and achieved successful gene therapy in dystrophic mice. In the current study, they set out to examine the feasibility and safety of the approach in larger animals. The research was funded in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI). The study was published on October 15, 2015, in Human Molecular Genetics.

To deliver the dystrophin microgene, the team used a common, widely studied viral vector known as AAV-9. They conducted the study in dystrophic young dogs, which have a body size similar to that of an affected boy, and which develop DMD in a similar manner as humans. They injected the microgene vector into the bloodstreams of 2 two-month-old dogs whose immune systems were transiently suppressed.

The researchers found that the dogs tolerated the injections well and that their growth wasn’t altered. The researchers detected the dystrophin protein in numerous muscles—including the limbs, diaphragm, and heart—for at least 4 months. Microscopic improvements could be seen in the muscle tissue as well.

“This is the most common muscle disease in boys, and there is currently no effective therapy,” Duan says. “This discovery took our research team more than 10 years, but we believe we are on the cusp of having a treatment for the disease.”

The group is further assessing the long-term safety and effectiveness of the gene therapy treatment in large mammals, as many significant obstacles remain.

—by Carol Torgan, Ph.D.