On a bright April morning in 1990, 9-year-old Sam Looper wiggled a toe on his left foot and made medical history. Toe wiggling is not usually cause for celebration, but in Sam's case, it was quite astounding, for he had Duchenne muscular dystrophy (DMD), and even this simple movement had been impossible for him.

It usually takes years for parents to realize that their son has DMD. The disease usually affects boys. At first the child is merely slow and clumsy, lagging behind playmates or having difficulty navigating stairs. Because his lower limb muscles appear firm and even prominent, concerned parents often do not suspect a muscular problem, yet already fat is filling in for progressively weakening muscles, making them appear deceptively robust.

A young child with DMD develops an odd but characteristic way of standing, pulling himself with his hands and gradually creeping to an erect stance. His calf muscles are too weak to power sitting and standing in the usual manner. This Gower sign usually alerts a physician, often during a routine physical exam, to suspect DMD. Laboratory tests confirm the diagnosis. Tests may reveal abnormal enzyme levels indicating muscle breakdown, or they may identify the abnormal gene that causes DMD. The gene is passed from the mother, who is a carrier, or arises in the boy as a spontaneous mutation (genetic change).

DMD causes progressive helplessness. The boy is typically wheelchair-bound by early adolescence and usually dies by age 20 of respiratory or heart failure, because smooth and cardiac muscle lack dystrophin too. Steroid drugs and exercise can forestall symptoms somewhat, but there is no cure.

This bleak prognosis prompted Sam Looper's family to allow him to undergo a controversial therapy. Sam received a transplant of his father's healthy, dystrophin-producing immature muscle cells (myoblasts) in four of his toes. If side effects arose, they hey would harm only a small part of his body. After the treatment, Sam could move his toes.

Sam's toe-wiggling ability was disappointing, however, for two reasons. First, the byoblasts do not migrate from where they are injected, so treating bodywide muscular dystrophy is difficult. Second, Sam's immune system attacked the transplanted cells, even though they came from a close relative.

To combat these problems, researchers in further trials implanted boys with myoblasts at many sites in their legs, thighs, and buttocks and gave them cyclosporine, a drug to prevent immune rejection. Scientists are not yet sure whether modest gains in strength seen in 43% of the treated muscles are due to the transplanted myoblasts or to the cyclosporine. Nor can myoblast implants in skeletal muscle treat the more life-threatening deficit in cardiac and smooth muscle. A bigger challenge is to add the needed dystrophin to muscles in and around vital organs, such as the heart, lungs, and digestive tract.