Duchenne Muscular Dystrophy Gene Therapy Restores All Muscles in Dogs

Researchers at the University of Missouri have reported the complete and successful treatment of Duchenne muscular dystrophy (DMD) in dogs through injection of a viral vector carrying a dystrophin micro gene, leading to recovery of all muscles. Clinical trials involving humans are being planned as a next step for the team. The research paper, entitled “Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus,” was published in Human Molecular Genetics.

Previous studies have successfully shown that gene delivery using an adenovirus effectively reached all muscles in the body in DMD mice models. But the robust results in gene therapy observed in rodents were never fully translated to larger animal models. One of the most important features for a possible DMD cure is its capacity to reach all afflicted tissues throughout the body. In this study, the MU research team demonstrated for the first time a successful and systemic gene delivery method in a DMD large mammal model.

The researchers injected dogs (aged two to three months old) with initial signs of DMD with an adeno-associated virus vectors carrying a microgene, a smaller version of the dystrophin gene, one of the largest in the human genome. The size of the dystrophin gene is a hurdle for an efficient gene therapy delivery, as it is very difficult to deliver the entire gene in a vector. However, this microgene, encoding a mini version of the dystrophin gene, had previously been able to reach and protect all muscles in a mice model of DMD. Now, after more than a decade designing the strategy, researchers have finally achieved success in dogs, where muscle function was improved and no adverse effects were observed. The dogs, now six to seven months old, continue to develop normally.

Researchers believe that early treatment, before serious damage inflicted by the disease, is essential for therapeutic success.

“This is the most common muscle disease in boys, and there is currently no effective therapy. 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,” commented Dr. Dongsheng Duan, lead researcher of the study, who was recently given a five-year, $3 million grant from the National Institutes of Health (NIH) to continue this promising research.