January 16, 2004

MUSCLE-DERIVED STEM CELLS SURVIVE,
MAKE DYSTROPHIN IN BOYS WITH DUCHENNE MD

Researchers in the Human Genetics Unit of Laval University in Quebec City have announced that three boys with Duchenne muscular dystrophy (DMD) began producing normal dystrophin after receiving muscle-derived stem cells from their fathers.

Dystrophin, the protein that’s missing from the muscle cell membrane in DMD, appeared in a small percentage of injected muscle fibers. The experiment also shows that the boys, ages 8-16, didn’t reject the donated cells.

Between 1990 and 1995, MDA sponsored five clinical trials to transplant immature, muscle-derived cells (sometimes called “myoblasts”) from healthy donors into boys with DMD. None of these trials showed any benefit, with few of the transplanted cells surviving.

This new experiment, conducted by Jacques Tremblay and colleagues, differs from earlier trials of muscle cell transplantation (sometimes called “myoblast transfer”) on a number of points, the investigators say. Tremblay received MDA funding for the lab experiments underlying the clinical trial.

In comparison to earlier experiments, larger numbers of muscle cells were injected, the injections were spaced more closely, the donor fathers were matched with their sons on measures of tissue compatibility, and a powerful immunosuppressant, tacrolimus, was given to the cell recipients.

The cells were isolated from the fathers’ arm muscles and subjected to laboratory tests to ensure that they could form muscle either by themselves or by fusing with existing muscle. They then were injected into the boys’ lower leg muscles.

Four weeks after the transplant, biopsies that removed the entire injected area -- 1 cubic centimeter (0.4 cubic inches) of tissue -- showed that the first boy was producing normal dystrophin in 9 percent of the fibers in the grafted section; the second produced it in 6.8 percent; and the third in 11 percent.

Because the injected area was very small, the researchers didn’t expect to see any functional improvement and didn’t test for it.

Tremblay said he was encouraged by the findings, which were published online Jan. 14 in the journal Molecular Therapy. He noted, however, that still more cells per area of muscle will have to be injected to get meaningful results.

His plans, if regulatory agencies in Canada approve them, include increasing the number of injections and ultimately transplanting cells into the entire biceps.

Tremblay said he’s confident that cell transplantation is “part of the solution” for treating DMD.