STEM CELLS WORK AGAINST MUSCULAR DYSTROPHY IN MICE,
MDA SCIENTISTS FIND

TUCSON, Ariz., July 10, 2003 — Scientists supported by the Muscular Dystrophy Association have shown for the first time that stem cells can prevent the effects of muscular dystrophy (MD) in mice.

Hundreds of thousands of Americans have some form of MD, a group of muscle-wasting diseases that have no cure and until now have proved intractable to stem cell therapy. When stem cells were injected directly into muscle or transplanted into bone marrow, in animals or in people, neither procedure has led to significant muscle regeneration.

The key to success appears to lie in a newly isolated type of stem cell that’s associated with blood vessels and can rapidly find its way to muscles when injected into an artery. In mice with MD, the cells – called mesoangioblasts – regenerated muscle and improved strength, with no sign of immune rejection.

Giulio Cossu at the University of Rome and the Stem Cell Research Institute in Milan, Italy, discovered the cells and tested them in mice developed by Kevin Campbell, an investigator of the Howard Hughes Institute, and a member of MDA’s Scientific Advisory Committee. Rita Barresi, an MDA grantee and postdoctoral fellow in Campbell’s lab at the University of Iowa in Iowa City, assisted in the analysis of the treated mice.

“This is a milestone in our stem cell research efforts,” said Sharon Hesterlee, MDA director of Research Development. “This group has overcome the two main hurdles we’ve faced: delivering stem cells to a large area of muscle tissue, and getting the cells to make enough healthy muscle to have a therapeutic effect.”

The team’s work was published online today by the journal Science.

The researchers first gave mesoangioblasts from normal mice to mice lacking alpha-sarcoglycan, the muscle protein flawed in people with limb-girdle MD type 2D. After a single injection into an artery in the hind leg, the cells migrated to several leg muscles, and alpha-sarcoglycan could be detected there for at least three months.

When the injections were given three times over four months, muscles in the injected leg showed less degeneration and less fibrosis (a buildup of fatty tissue), and the individual fibers were stronger than those of untreated mice. The treated mice were also better at staying on a spinning rod.

The scientists also removed mesoangioblasts from mice with alpha-sarcoglycan deficiency and used a virus to give the cells an intact alpha-sarcoglycan gene. Those cells were as effective as normal cells when injected into the mice.

The results suggest that people with MD could be treated with mesoangioblasts derived from a donor or from their own blood vessels, Campbell said.

He and Cossu are testing the cells in mice with other forms of MD, and attempting to find their counterparts in adult human tissue. The cells need to be tested in larger animals before human trials can be designed, Campbell said.

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association also provides comprehensive health care and support services, advocacy and education. The Association’s programs are funded almost entirely by individual private contributors.