Team Pursues Cell Transplants In DMD, BMD

Jacques Tremblay at Laval University in Quebec City says he has obtained permission from Health Canada to conduct a clinical trial to see whether transplantation of muscle precursor cells (MPCs) can improve the strength of an arm muscle in 10 males with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) who are at least 18 years old.

Tremblay, who received MDA support to develop laboratory procedures associated with MPCs in the late 1990s and in 2004, has previously shown that dystrophin (the protein needed in DMD) was produced in the muscle fibers of eight out of nine patients who received transplantations of this type of cell.

The new trial will utilize a technique his lab recently developed called high-density cell transplantation, which allows millions of cells per square centimeter to be injected at a time.

In January, in the journal of Neuromuscular Disorders, Tremblay’s group reported they had used the high-density technique successfully in a 26-year-old man with advanced DMD, who tolerated the procedure well and may even have benefited somewhat from it.

They used cells isolated from an arm muscle of the patient’s father and then prepared in the lab to the point where they were on their way to becoming muscle but weren’t fully mature. They then injected 67.5 million MPCs per square centimeter into a lower leg muscle, 55 million per square centimeter in to the area below the thumb, and 25 million per square centimeter into the biceps muscle.

The patient, who was given the immunosuppressant drug tacrolimus (Prograf) to prevent rejection of the cells, said he found the injections were more tolerable than the average dental procedure.

A year and a half after the transplant, some 35 percent of the injected muscle fibers in the leg were making dystrophin. In the biceps, where there was more scar tissue, there were only a few fibers left, two of which were making dystrophin.

The only functional improvement the team saw was a significant increase in the patient’s ability to move his thumb. They say this may have been a placebo effect [a favorable response to a treatment because the patient believes in it], since the subject knew he was receiving MPCs.

The new trial, Tremblay notes, will be “blinded,” meaning one arm will get MPCs and the other a salt solution. Neither the investigators nor the participants will know which arm got which preparation.

Tremblay says progress in his lab can be followed on the Jacques P. Tremblay lab site.