Duchenne muscular dystrophy (DMD) is the most common and, sadly, the most severe form of the debilitating genetic disorder. Now researchers have used a new gene therapy technique to restore muscle strength and stabilize the symptoms of the disorder in dogs, in an important step that could one day lead to the treatment being applied to children.
Affecting one in 5,000 boys (but very rarely occurring in girls), DMD usually begins to show itself around the age of three to five, and progresses quickly from there. It disrupts dystrophin, a protein that's responsible for maintaining muscle integrity and strength. As a result, DMD causes the muscles to weaken and waste away, often rendering a patient unable to walk by age 12 and unlikely to live beyond their mid-20s.
To combat genetic disorders, researchers often insert a healthy copy of the affected gene into a viral vector – essentially, a harmless shell of a virus that carries the material into cells. Unfortunately, that tactic doesn't work with DMD: the gene contains 2.3 million base pairs, making it far too big a load for a viral vector.
To get around this problem, researchers from the Généthon laboratory at AFM-Téléthon and the Royal Holloway University of London developed microdystrophin, a shortened version of the dystrophin gene that contains only about 4,000 base pairs. When this is combined with a viral vector and injected into a patient, functional proteins are once again produced.
The scientists tested their new gene therapy technique on 12 Golden Retrievers that were naturally affected by DMD. They injected microdystrophin into the animals intravenously, and observed them for more than two years afterwards. After just one dose, the researchers noted that dystrophin production returned to normal, significantly restoring muscle function in the dogs and stabilizing their other symptoms without any side effects.
This is the first time such a treatment has been seen in large animals, and given the similarities in symptoms and size between dogs and children, this success raise hopes for an eventual human treatment.
"This preclinical study demonstrates the safety and efficacy of microdystrophin, and makes it possible to consider developing a clinical trial in patients," says Caroline Le Guiner, main author of the the study. "Indeed, this is the first time that it has been possible to treat the whole body of a large-sized animal with this protein. Moreover, this innovative approach allows treatment of all patients with Duchenne muscular dystrophy, regardless of the genetic mutation responsible."
The research was published in the journal Nature Communications.