Articulo original: http://www.newscientist.com/channel/health/mg19225780.143-stem-cells-reverse-muscular-dystrophy.html

Stem cells reverse muscular dystrophy
15 November 2006
NewScientist.com news service
Debora Mackenzie

STEM cells have helped dogs with muscular dystrophy to walk again. Doctors hope a similar approach in humans could lead to more complete improvement than the other leading contender for a cure - an RNA-blocking drug now in clinical trials.

Duchenne muscular dystrophy (DMD) strikes about one in 35,000 children, almost always boys, and is usually fatal by the age of 30. It is caused by mutations in the gene for the muscle protein dystrophin. Without it, muscle contractions shear and kill muscle cells, and victims become progressively weaker, often dying when their breathing muscles fail.

Giulio Cossu and colleagues at the San Raffaele Scientific Institute in Milan, Italy, had found previously that adult stem cells called mesangioblasts colonise muscle and restore dystrophin production in mice engineered to lack the gene. But the therapeutic effect could not be tested, because these mice do not develop MD.

Dogs do. So Cossu's team took mesangioblasts from golden retrievers with a mutation in the dystrophin gene that causes a disease similar to DMD. They used gene therapy to give the cells a normal version of the gene, before reinjecting them into the dogs' leg arteries. They also transplanted mesangioblasts from healthy dogs into dogs with MD, and gave drugs to suppress immune rejection (Nature, DOI: 10.1038/nature05282).

Repeated doses of cells from normal donors restored muscle function in four of five dogs. All four lived for more than a year after the experiment, unlike controls, and initially regained the ability to walk, though two relapsed. The cells colonised muscle and produced dystrophin, not just in the injected leg but elsewhere, including the diaphragm. "That is important, because respiratory muscles are very difficult to target with direct injection," says Johnny Huard of the University of Pittsburgh in Pennsylvania, who has also studied stem cells and MD.

Unfortunately the dog's own modified stem cells did not restore muscle function, although they did produce dystrophin. They would be preferable to donor cells, as they would not risk rejection. "The work shows these cells are feasible, but need to be improved," says Huard.

Cossu plans to repeat the experiment with growth factors to encourage more of the dogs' own cells to colonise muscle. The team also hopes to conduct human trials using matched donor cells.

Until now, efforts to treat DMD have largely focused on silencing the dystrophin mutation. PTC Therapeutics in South Plainfield, New Jersey, has developed a drug for one type of mutation by making the translation machinery skip it. This results in a slightly altered dystrophin protein that is at least functional, if not as good as the normal version. The drug is being tested in DMD patients.