Speakers at an MDA-sponsored workshop held June 14 in Tucson, Ariz., as part of a larger meeting of the Federation of American Societies for Experimental Biology (FASEB), presented a variety of reports about muscle stem cell experiments and clinical trials.
Louis Kunkel, molecular geneticist and MDA grantee at Children's Hospital of Boston, revisited the myoblast transfer trials of the early 1990s.
In these trials, several MDA-supported research groups injected immature muscle cells (myoblasts) into the muscles of children with Duchenne muscular dystrophy (DMD). The procedure showed no benefit in the children, but some of the transplanted cells appeared to survive and to produce dystrophin, the protein needed in DMD.
|Jacques Tremblay. Photo by Ron Medvescek|
Kunkel emphasized that the trials should be considered informative phase 1 trials intended to see whether transplanting donor cells in MD was feasible and safe.
The transplanted cells were not the right cells to do what we expected them to do, Kunkel said. But the studies showed safety and efficacy of this type of procedure and could be built on, using additional knowledge available today.
Jacques Tremblay of the Universite Laval in Quebec, who has received MDA funding to improve myoblast transfer, described a trial in which nine boys with DMD received donated immature muscle cells from their parents and also received tacrolimus, a potent new immunosuppressant.
Tremblay's group injected the cells into a small area in a lower leg muscle. In eight boys, between 3.5 and 26 percent of the fibers in the injected area produced dystrophin.
Gillian Butler-Browne, a British researcher at INSERM in Paris, described a trial in which people with oculopharyngeal MD (OPMD) received cell transplants from their stronger muscles to their weaker ones.
|Mark Fiszman. Photo by Ron Medvescek|
The researchers selected people with OPMD and severe pharyngeal (throat) muscle weakness with great difficulty in swallowing. They took cells from the person's functionally unaffected thigh or chest muscles and injected them into the pharyngeal muscles. Six months after the procedures, the patients' swallowing appeared better.
The researchers say that, with time, the transplanted cells may weaken in the throat environment. Still, Butler-Browne noted, the transplant may buy some time during which people with OPMD can comfortably eat and drink.
Mark Fiszman, also at INSERM, said his group plans to try the same approach in people with facioscapulohumeral MD.
Daniel Garry, an MDA grantee at the University of Texas Southwestern Medical Center in Dallas, described research on the possibility of stem cell treatment of cardiac damage in muscular dystrophy.
Garry said that the heart is capable of limited regeneration compared to that of skeletal muscle. Though cardiac muscle stem cells have been identified in the heart, it isn't clear that these cells can become functional cardiac cells.
There are significant immunological barriers to using cells other than the patient's own, he said, but industry isn't likely to pursue the customized cell harvesting and processing that would be needed if each person's own cells were to be used.
Elizabeth McNally, a cardiologist and MDA grantee studying bone marrow transplantation in mouse models of limb-girdle MD (LGMD) at the University of Chicago, added that clinical trials in this area need to be conducted with clear, unambiguous markers that can tell the investigators whether the donor-derived cells have survived in the recipients heart's and whether they matured into heart cells.
She also cautioned that the risk of heart rhythm abnormalities from transplanting cells that might not connect properly to the existing heart tissue is enormous.