Duchenne Muscular dystrophy (DMD) is a degenerative disease that afflicts young boys and is one of the most prevalent forms of muscular dystrophy. A defect in the gene for the cytoplasmic protein dystrophin leads to progressive loss in muscle function in these patients, cutting short their lives to a few decades. However, a recent study in a canine model of DMD by researchers at Boston Children's Hospital (Boston, MA) reveals that it might be possible to have this congenital defect and still lead a normal life (Cell 163, 1204–1213; 2015).

DMD is difficult to study, primarily owing to its rapid lethality and lack of animal models that mirror the symptoms seen in humans. Golden Retriever Muscular Dystrophy (GRMD) dogs, carrying the classic dystrophin mutation, make an excellent model system for DMD studies. These animals model the symptoms and disease progression seen in humans and typically have lifespans of only 2 years. In their study, Louis M. Kunkel and colleagues performed genetic analysis on two exceptional GRMD dogs that are able to walk, run and live a normal lifespan despite carrying the dystrophin mutation. Taking a closer look at these 'escaper' dogs, “We asked, what did the father pass to the escaper that made him able to escape the disease?'” says Natassia M. Vieira, first author of the study.

The answer lies deep in the genome of the escapers. Combining techniques such as genome-wide association studies and gene expression analysis, the scientists narrowed down the difference to a single nucleotide change in the gene Jagged 1. This change, located in the promoter sequence of the gene, was present only in the escaper dogs and resulted in a heightened expression of Jagged1 in their muscles. The muscles still underwent the same amount of wear and tear due to the dysfunction in dystrophin, but the higher Jagged1 levels improved the capacity for muscle repair. Engineering this change in a zebrafish model of DMD also led to a dramatic recovery of muscle function in the fish.

Most therapies for DMD focus on over-expressing dystrophin or its homologs in the patients. This study gives insight into the hitherto unexplored dynamics of muscle damage and repair at play in DMD. Manipulating Jagged1 activity in conjunction with gene therapy might open the doors to a longer and healthier life for DMD patients.