Lead Author

Giulio Cossu has devoted the past 15 years to the search for a treatment for muscular dystrophy. On page 574, he and his colleagues reveal what they believe could be a breakthrough. Cossu, based at the San Raffaele Scientific Institute in Milan, Italy, and his team have found that a type of stem cell called a mesoangioblast, which is extracted from the aorta of embryos, could be the basis of a treatment. They show how the cells allowed golden retrievers with the crippling genetic disorder to walk and even jump again — tantalizing findings that may one day lead to a human therapy.

Why test these stem cells on dogs?

There are no models of muscular dystrophy in primates. Golden retriever animal models are the best to date, because their size and general physiology is closest to humans.

Cell therapy seemed to hold little promise for muscular dystrophy. Why did you go on?

Finding the mesoangioblast stem cell was the winning point. These stem cells can cross the membrane of blood vessels and distribute themselves evenly through the downstream muscles — something that was not possible for other stem cells such as satellite cells, which would have to be injected into every 2 millimetres of muscle in the body. That would have meant thousands of injections.

What were the most surprising results?

One of the most emotional moments I had was when I saw the severely impaired dog running again. I couldn't have anticipated it going so well. I hope that this result can be transferred to humans.

Donor stem cells from healthy dogs worked better than genetically corrected cells from the afflicted patient dog. Why?

We think it mainly has to do with the micro-dystrophin used to deliver the patient dog's cells. Dystrophin is the protein that creates an elastic scaffold able to absorb the stress during muscle contraction. Donor cells from a normal dog express a dystrophin gene that makes a complete, functional protein. As dystrophin is a large protein that does not fit into most viral vectors, we used a micro-dystrophin that encodes a small version of the same protein. It showed promise in mice, but didn't work that well in dogs.

What will it take to start human trials?

First, we'll have a longer follow-up in dogs. We'll treat them like humans, continuing the administration of an immunosuppressive agent such as cyclosporine to avoid rejection of the foreign cells. Once we get the money and decide on a strategy, it will be about three years before human clinical trials.